The Population-level Effect of Adjuvant Therapies on Breast Cancer Recurrence: Application of the Trend-in-Trend Design.

PURPOSE: Breast cancer has an average 10-year relative survival reaching 84%. This favorable survival is due, in part, to the introduction of biomarker-guided therapies. We estimated the population-level effect of the introduction of two adjuvant therapies-tamoxifen and trastuzumab-on recurrence using the trend-in-trend pharmacoepidemiologic study design. METHODS: We ascertained data on women diagnosed with nonmetastatic breast cancer who were registered in the Danish Breast Cancer Group clinical database. We used the trend-in-trend design to estimate the population-level effect of the introduction of (1) tamoxifen for postmenopausal women with estrogen receptor (ER)-positive breast cancer in 1982, (2) tamoxifen for premenopausal women diagnosed with ER-positive breast cancer in 1999, and (3) trastuzumab for women <60 years diagnosed with human epidermal growth factor receptor 2-positive breast cancer in 2007. RESULTS: For the population-level effect of the introduction of tamoxifen among premenopausal women diagnosed with ER-positive breast cancer in 1999, the risk of recurrence decreased by nearly one-half (OR = 0.52), consistent with evidence from clinical trials; however, the estimate was imprecise (95% confidence interval [CI] = 0.25, 1.85). We observed an imprecise association between tamoxifen use and recurrence from the time it was introduced in 1982 (OR = 1.24 95% CI = 0.46, 5.11), inconsistent with prior knowledge from clinical trials. For the introduction of trastuzumab in 2007, the estimate was also consistent with trial evidence, though imprecise (OR = 0.51; 95% CI = 0.21, 22.4). CONCLUSIONS: We demonstrated how novel pharmacoepidemiologic analytic designs can be used to evaluate the routine clinical care and effectiveness of therapeutic advancements in a population-based setting while considering some limitations of the approach.

Defining Undertreatment and Overtreatment in Older Adults With Cancer: A Scoping Literature Review.

PURPOSE: The terms undertreatment and overtreatment are often used to describe inappropriate management of older adults with cancer. We conducted a comprehensive scoping review of the literature to clarify the meanings behind the use of the terms. METHODS: We searched PubMed (National Center for Biotechnology Information), Embase (Elsevier), and CINAHL (EBSCO) for titles and abstracts that included the terms undertreatment or overtreatment with regard to older adults with cancer. We included all types of articles, cancer types, and treatments. Definitions of undertreatment and overtreatment were extracted, and categories underlying these definitions were derived through qualitative analysis. Within a random subset of articles, C.D. and K.P.L. independently performed this analysis to determine final categories and then independently assigned these categories to assess inter-rater reliability. RESULTS: Articles using the terms undertreatment (n = 236), overtreatment (n = 71), or both (n = 51) met criteria for inclusion in our review (n = 256). Only 14 articles (5.5%) explicitly provided formal definitions; for the remaining, we inferred the implicit definitions from the terms' surrounding context. There was substantial agreement (κ = 0.81) between C.D. and K.P.L. in independently assigning categories of definitions within a random subset of 50 articles. Undertreatment most commonly implied less than recommended therapy (148; 62.7%) or less than recommended therapy associated with worse outcomes (88; 37.3%). Overtreatment most commonly implied intensive treatment of an older adult in whom the harms of treatment outweigh the benefits (38; 53.5%) or intensive treatment of a cancer not expected to affect an older adult in his/her remaining lifetime (33; 46.5%). CONCLUSION: Undertreatment and overtreatment of older adults with cancer are imprecisely defined concepts. We propose new, more rigorous definitions that account for both oncologic factors and geriatric domains.

Metabolic Pathway Analysis and Effectiveness of Tamoxifen in Danish Breast Cancer Patients.

BACKGROUND: Tamoxifen and its metabolites compete with estrogen to occupy the estrogen receptor. The conventional dose of adjuvant tamoxifen overwhelms estrogen in this competition, reducing breast cancer recurrence risk by nearly half. Phase I metabolism generates active tamoxifen metabolites, and phase II metabolism deactivates them. No earlier pharmacogenetic study has comprehensively evaluated the metabolism and transport pathways, and no earlier study has included a large population of premenopausal women. METHODS: We completed a cohort study of 5,959 Danish nonmetastatic premenopausal breast cancer patients, in whom 938 recurrences occurred, and a case-control study of 541 recurrent cases in a cohort of Danish predominantly postmenopausal breast cancer patients, all followed for 10 years. We collected formalin-fixed paraffin-embedded tumor blocks and genotyped 32 variants in 15 genes involved in tamoxifen metabolism or transport. We estimated conventional associations for each variant and used prior information about the tamoxifen metabolic path to evaluate the importance of metabolic and transporter pathways. RESULTS: No individual variant was notably associated with risk of recurrence in either study population. Both studies showed weak evidence of the importance of phase I metabolism in the clinical response to adjuvant tamoxifen therapy. CONCLUSIONS: Consistent with prior knowledge, our results support the role of phase I metabolic capacity in clinical response to tamoxifen. Nonetheless, no individual variant substantially explained the modest phase I effect on tamoxifen response. IMPACT: These results are consistent with guidelines recommending against genotype-guided prescribing of tamoxifen, and for the first time provide evidence supporting these guidelines in premenopausal women.

Cohort Profile: the Predictors of Breast Cancer Recurrence (ProBe CaRE) Premenopausal Breast Cancer Cohort Study in Denmark.

PURPOSE: The Predictors of Breast Cancer Recurrence (ProBe CaRe) study was established to evaluate modification of tamoxifen (TAM) effectiveness in premenopausal women through reduced activity of TAM-metabolising enzymes. It comprehensively evaluates the effects of pharmacogenetic variants, use of concomitant medications and biomarkers involved in oestrogen metabolism on breast cancer recurrence risk. PARTICIPANTS: The ProBe CaRe study was established using resources from the Danish Breast Cancer Group (DBCG), including 5959 premenopausal women diagnosed with stage I-III primary breast cancer between 2002 and 2010 in Denmark. Eligible participants were divided into two groups based on oestrogen receptor alpha (ERα) expression and receipt of TAM therapy, 4600 are classified as ERα+/TAM+ and 1359 are classified as ERα-/TAM-. The ProBe CaRe study is a population-based cohort study nested in a nearly complete source population, clinical, tumour and demographic data were abstracted from DBCG registry data. Linkage to Danish registries allows for abstraction of information regarding comorbid conditions, comedication use and mortality. Formalin-fixed paraffin-embedded tissue samples have been prepared for DNA extraction and immunohistochemical assay. FINDINGS TO DATE: To mitigate incorrect classification of patients into specific categories, we conducted a validation substudy. We compared data acquired from registry and from medical record review to calculate positive predictive values (PPVs) and negative predictive values. We observed PPVs near 100% for tumour size, lymph node involvement, receptor status, surgery type, receipt of radiotherapy, receipt of chemotherapy and TAM treatment. We found that the PPVs were 96% (95% CI 83% to 100%) for change in endocrine therapy and 61% (95% CI 42% to 77%) for menopausal transition. FUTURE PLANS: The ProBeCaRe cohort study is well positioned to comprehensively examine pharmacogenetic variants. We will use a Bayesian pathway analysis to evaluate the complete TAM metabolic path to allow for gene-gene interactions, incorporating information of other important patient characteristics.

Health-Related Quality of Life in a Predictive Model for Mortality in Older Breast Cancer Survivors.

OBJECTIVES: To develop a predictive model and risk score for 10-year mortality using health-related quality of life (HRQOL) in a cohort of older women with early-stage breast cancer. DESIGN: Prospective cohort. SETTING: Community. PARTICIPANTS: U.S. women aged 65 and older diagnosed with Stage I to IIIA primary breast cancer (N=660). MEASUREMENTS: We used medical variables (age, comorbidity), HRQOL measures (10-item Physical Function Index and 5-item Mental Health Index from the Medical Outcomes Study (MOS) 36-item Short-Form Survey; 8-item Modified MOS Social Support Survey), and breast cancer variables (stage, surgery, chemotherapy, endocrine therapy) to develop a 10-year mortality risk score using penalized logistic regression models. We assessed model discriminative performance using the area under the receiver operating characteristic curve (AUC), calibration performance using the Hosmer-Lemeshow test, and overall model performance using Nagelkerke R2 (NR). RESULTS: Compared to a model including only age, comorbidity, and cancer stage and treatment variables, adding HRQOL variables improved discrimination (AUC 0.742 from 0.715) and overall performance (NR 0.221 from 0.190) with good calibration (p=0.96 from HL test). CONCLUSION: In a cohort of older women with early-stage breast cancer, HRQOL measures predict 10-year mortality independently of traditional breast cancer prognostic variables. These findings suggest that interventions aimed at improving physical function, mental health, and social support might improve both HRQOL and survival.

False-positive mammography and its association with health service use.

OBJECTIVES: A false-positive mammogram can result in anxiety, distress, and increased perceptions of breast cancer risk, potentially changing how women utilize healthcare. This study examined whether having an abnormal mammogram, considered a proxy for elevated risk perception, was associated with greater future health service use (outpatient visits and referrals). STUDY DESIGN: A retrospective cohort study using electronic health record data, spanning 2008 to 2012, from Boston Medical Center, a safety-net hospital. METHODS: We grouped 3920 women aged 40 to 75 years receiving primary care and who had a mammogram between 2010 and 2011 into 3 categories: false-positive mammogram at index date; previous false positive, but normal index mammogram; and no history of false-positive mammograms. We contrasted the longitudinal changes in outpatient visits and provider referrals, before versus after the index mammogram, between women with false-positive mammogram and those without using Poisson regression models with a difference-in-differences specification. Clinical, visit, and demographic data were obtained from the institutional clinical data warehouse. RESULTS: Adjusting for baseline differences in sociodemographic characteristics across risk groups and for secular changes between pre- and postindex periods, a current false-positive mammogram was associated with an 18% increase in overall outpatient visits (incidence rate ratio [IRR], 1.18; 95% CI, 1.07-1.51), but no corresponding increase in provider referrals (IRR, 1.15; 95% CI, 0.99­1.34), relative to never having a false positive. A previous false-positive mammogram had no associated change in outpatient utilization (IRR, 0.99; 95% CI, 0.91-1.07). CONCLUSIONS: Providers should discuss the implications of mammography findings at the time of screening to help mitigate potential detrimental effects and promote appropriate engagement in health services.

Self-Reported Function More Informative than Frailty Phenotype in Predicting Adverse Postoperative Course in Older Adults.

BACKGROUND/OBJECTIVE: Current preoperative assessment tools such as the American College of Surgeons Surgical Risk Calculator (ACS Calculator) are suboptimal for evaluating older adults. The objective was to evaluate and compare the performance of the ACS Calculator for predicting risk of serious postoperative complications with the addition of self-reported physical function versus a frailty score. DESIGN: Prospective cohort. SETTING: Two tertiary care academic medical centers in Massachusetts. PARTICIPANTS: Individuals aged 65 and older undergoing any surgery with a risk of serious complication of 5% or greater (N = 403). MEASUREMENTS: We measured self-reported physical function using the Late-Life Function and Disability Instrument (LLFDI FUNCTION) and frailty phenotype (FP), which has a score ranging from 0 to 5 based on slow gait speed, weak handgrip, exhaustion, weight loss, or low activity. Using c-statistic and net classification improvement (NRI), we then analyzed capability of LLFDI-FUNCTION versus FP to improve the ACS Calculator for predicting an adverse postoperative course (serious complication, discharge to nursing home, readmission, death within 30 days of surgery). Increase in c-statistic and net reclassification improvement (NRI) for LLFDI-FUNCTION versus FP in addition to the ACS Calculator for predicting an adverse postoperative course (serious complication, discharge to nursing home, readmission, death within 30 days of surgery) RESULTS: Over 30 days, 26% of participants developed an adverse postoperative course. The increase in c-statistic for the ACS Calculator (baseline value 0.645) was slightly greater with LLFDI-FUNCTION (0.076) than with FP (0.058), with a bootstrapped difference in c-statistic of 0.005 (95% confidence interval = 0.002-0.007). NRI was also better with LLFDI-FUNCTION. CONCLUSION: The LLFDI-FUNCTION predicted postoperative complications slightly better than the FP. Further studies are needed to confirm these findings and validate the use of the LLFDI-FUNCTION with the ACS Calculator for preoperative assessments of older adults.

Validity of Danish Breast Cancer Group (DBCG) registry data used in the predictors of breast cancer recurrence (ProBeCaRe) premenopausal breast cancer cohort study.

BACKGROUND: Validation studies of the Danish Breast Cancer Group (DBCG) registry show good agreement with medical records for adjuvant treatment data, but inconsistent recurrence information. No studies have validated changes in menopausal status or endocrine therapy during follow-up. In a longitudinal study, we validated DBCG data using medical records as the gold standard. MATERIAL AND METHODS: From a cohort of 5959 premenopausal women diagnosed during 2002-2010 with stage I-III breast cancer, we selected 151 patients - 77 estrogen-receptor-positive and 74 estrogen-receptor-negative - from three hospitals. We assessed the validity of DBCG registry data on patient, tumor, and treatment factors, and follow-up information on menopausal transition, changes in endocrine therapy, and recurrence. We computed positive predictive values (PPVs) with 95% confidence intervals (95%CI). RESULTS: Agreement was near perfect for tumor size, lymph node involvement, receptor status, surgery type, and receipt of radiotherapy, chemotherapy, or tamoxifen treatment. The PPV for a change in endocrine therapy in the DBCG was 96% (95%CI = 83, 100). The PPV for menopausal transition was 61% (95%CI = 42, 77). The PPV for DBCG-recorded recurrence was 100%. However, of 19 patients who had a recurrence documented in their medical record, 13 had the recurrence registered in DBCG. CONCLUSIONS: DBCG data are valid for most epidemiological studies of breast cancer treatment. Data on menopausal transition may be less valid, though this interpretation depends on the suitability of medical records for making this assessment. Although recurrence is missing for some, this would not bias most ratio measures of association.

Motivation and mortality in older women with early stage breast cancer: A longitudinal study with ten years of follow-up.

OBJECTIVES: The Getting Out of Bed Scale (GOB) was validated as a health-related quality of life (HRQoL) variable in older women with early stage breast cancer, suggesting its potential as a concise yet powerful measure of motivation. The aim of our project was to assess the association between GOB and mortality over 10years of follow-up. MATERIALS AND METHODS: We studied 660 women ≥65-years old diagnosed with stage I-IIIA primary breast cancer. Data were collected over 10years of follow-up from interviews, medical records, and death indexes. RESULTS: Compared to women with lower GOB scores, women with higher GOB had an unadjusted hazard ratio (HR) of all-cause mortality of 0.78 at 5years, 95% confidence interval (CI) (0.52, 1.19) and 0.77 at 10years, 95%CI (0.59, 1.00). These associations diminished after adjusting for age and stage of breast cancer, and further after adjusting for other HRQoL variables including physical function, mental health, emotional health, psychosocial function, and social support. Unadjusted HRs of breast cancer-specific mortality were 0.92, 95%CI (0.49, 1.74), at 5years, and 0.82, 95%CI (0.52, 1.32), at 10years. These associations also decreased in adjusted models. CONCLUSION: Women with higher GOB scores had a lower hazard of all-cause mortality in unadjusted analysis. This effect diminished after adjusting for confounding clinical and HRQoL variables. GOB is a measure of motivation that may not be independently associated with cancer mortality, but reflects other HRQoL variables making it a potential outcome to monitor in older patients with cancer.

NCCN Guidelines Insights: Older Adult Oncology, Version 2.2016.

Cancer is the leading cause of death in older adults aged 60 to 79 years. Older patients with good performance status are able to tolerate commonly used treatment modalities as well as younger patients, particularly when adequate supportive care is provided. For older patients who are able to tolerate curative treatment, options include surgery, radiation therapy (RT), chemotherapy, and targeted therapies. RT can be highly effective and well tolerated in carefully selected patients, and advanced age alone should not preclude the use of RT in older patients with cancer. Judicious application of advanced RT techniques that facilitate normal tissue sparing and reduce RT doses to organs at risk are important for all patients, and may help to assuage concerns about the risks of RT in older adults. These NCCN Guidelines Insights focus on the recent updates to the 2016 NCCN Guidelines for Older Adult Oncology specific to the use of RT in the management of older adults with cancer.

Predicting 5- and 10-year survival in older women with early-stage breast cancer: self-rated health and walking ability.

OBJECTIVES: To determine life expectancy for older women with breast cancer. DESIGN: Prospective longitudinal study with 10 years of follow-up data. SETTING: Hospitals or collaborating tumor registries in four geographic regions (Los Angeles, California; Minnesota; North Carolina; Rhode Island). PARTICIPANTS: Women aged 65 and older at time of breast cancer diagnosis with Stage I to IIIA disease with measures of self-rated health (SRH) and walking ability at baseline (N = 615; 17% aged ≥80, 52% Stage I, 58% with ≥2 comorbidities). MEASUREMENTS: Baseline SRH, baseline self-reported walking ability, all-cause and breast cancer-specific estimated probability of 5- and 10-year survival. RESULTS: At the time of breast cancer diagnosis, 39% of women reported poor SRH, and 28% reported limited ability to walk several blocks. The all-cause survival curves appear to separate after approximately 3 years, and the difference in survival probability between those with low SRH and limited walking ability and those with high SRH and no walking ability limitation was significant (0.708 vs 0.855 at 5 years, P ≤ .001; 0.300 vs 0.648 at 10 years, P < .001). There were no differences between the groups in breast cancer-specific survival at 5 and 10 years (P = .66 at 5 years, P = .16 at 10 years). CONCLUSION: The combination of low SRH and limited ability to walk several blocks at diagnosis is an important predictor of worse all-cause survival at 5 and 10 years. These self-report measures easily assessed in clinical practice may be an effective strategy to improve treatment decision-making in older adults with cancer.

Why are U.S. girls getting meningococcal but not human papilloma virus vaccines? Comparison of factors associated with human papilloma virus and meningococcal vaccination among adolescent girls 2008 to 2012.

BACKGROUND: Human papilloma virus (HPV) vaccination rates in the United States remain low, compared with other recommended adolescent vaccines. We compared factors associated with intention to receive and receipt of HPV and meningococcal vaccines and completion of the HPV vaccine series among U.S. adolescent girls. METHODS: Secondary analysis of data from the National Immunization Survey-Teen for 2008 through 2012 was performed. Multivariable logistic modeling was used to determine factors associated with intent to receive and receipt of HPV and meningococcal vaccination, completion of the HPV vaccine series among girls who started the series, and receipt of HPV vaccination among girls who received meningococcal vaccination. FINDINGS: Provider recommendation increased the odds of receipt and intention to receive both HPV and meningococcal vaccines. Provider recommendation was also associated with a three-fold increase in HPV vaccination among girls who received meningococcal vaccination (p<.001), indicating a relationship between provider recommendation and missed vaccine opportunities. However, White girls were 10% more likely to report provider recommendation than Black or Hispanic girls (p<.01), yet did not have higher vaccination rates, implying a role for parental refusal. No factors predicted consistently the completion of the HPV vaccine series among those who started. CONCLUSION: Improving provider recommendation for co-administration of HPV and meningococcal vaccines would reduce missed opportunities for initiating the HPV vaccine series. However, different interventions may be necessary to improve series completion.

Knee osteoarthritis and frailty: findings from the Multicenter Osteoarthritis Study and Osteoarthritis Initiative.

BACKGROUND: Knee osteoarthritis (OA) and frailty are two conditions that are associated with functional limitation and disability in elders, yet their relation to one another is not known. METHODS: We included participants from two large, multicenter studies enriched with community dwelling older adults with knee OA (Multicenter Osteoarthritis Study and Osteoarthritis Initiative). Knee OA was defined radiographically (ROA) and symptomatically (SOA). Frailty was defined using the Study of Osteoporotic Fracture index as the presence of ≥2 of the following: (i) weight loss >5% between two consecutive visits; (ii) inability to arise from chair five times without support; (iii) poor energy. Cross-sectional and longitudinal associations of knee OA with prevalent and incident frailty, respectively, were examined using binomial regression with robust variance estimation, adjusting for potential confounders. RESULTS: In the cross-sectional analyses, frailty was more prevalent among participants with ROA (4.39% vs 2.77%; PR 1.60 [1.07, 2.39]) and SOA (5.88% vs 2.79%; PR 1.92 [1. 35, 2.74]) compared with those without ROA or SOA, respectively. In the longitudinal analyses, risk of developing frailty was greater among those with ROA (4.73% vs 2.50%; RR 1.45 [0.91, 2.30]) and SOA (6.30% vs 2.83%; RR 1.66 [1.11, 2.48]) than those without ROA or SOA, respectively. CONCLUSIONS: Knee OA is associated with greater prevalence and risk of developing frailty. Understanding the mechanisms linking these two common conditions of older adults would aid in identifying novel targets for treatment or prevention of frailty.

Older women's experience with a benign breast biopsy­a mixed methods study.

BACKGROUND: Little is known about older women's experience with a benign breast biopsy. OBJECTIVES: To examine the psychological impact and experience of women ≥ 65 years of age with a benign breast biopsy. DESIGN: Prospective cohort study using quantitative and qualitative methods. SETTING: Three Boston-based breast imaging centers. PARTICIPANTS: Ninety-four English-speaking women ≥ 65 years without dementia referred for breast biopsy as a result of an abnormal mammogram, not aware of their biopsy results at baseline, and with a subsequent negative biopsy. MEASUREMENTS: We interviewed women at the time of breast biopsy (before women knew their results) and 6 months post-biopsy. At both interviews, participants completed the validated negative psychological consequences of screening mammography questionnaire (PCQ, scores range from 0 to 36 [high distress], PCQ ≥ 1 suggests a psychological consequence, PCQs <1 are reported at time of screening) and women responded to open-ended questions about their experience. At follow-up, participants described the quality of information received after their benign breast biopsy. We used a linear mixed effects model to examine if PCQs declined over time. We also reviewed participants' open-ended comments for themes. RESULTS: Overall, 88% (83/94) of participants were non-Hispanic white and 33% (31/94) had a high-school degree or less. At biopsy, 76% (71/94) reported negative psychological consequences from their biopsy compared to 39% (37/94) at follow-up (p < 0.01). In open-ended comments, participants noted the anxiety (29%, 27/94) and discomfort (28%, 26/94) experienced at biopsy (especially from positioning on the biopsy table). Participants requested more information to prepare for a biopsy and to interpret their negative results. Forty-four percent (39/89) reported at least a little anxiety about future mammograms. CONCLUSIONS: The high psychological burden of a benign breast biopsy among older women significantly diminishes with time but does not completely resolve. To reduce this burden, older women need more information about undergoing a breast biopsy.

An oral health study of centenarians and children of centenarians.

OBJECTIVES: To determine whether oral health is better in centenarians than in a published birth cohort-matched sample and to compare oral health in centenarian offspring with a case-controlled reference sample. DESIGN: Observational cross-sectional study. SETTING: New England Centenarian Study (NECS). PARTICIPANTS: Seventy-three centenarians, 467 offspring, and 251 offspring generation-reference cohort subjects from the NECS. MEASUREMENTS: A self-report questionnaire was administered to measure oral health in all three groups, with edentulous rate as the primary outcome measure. The NECS made information on sociodemographic characteristics and medical history available. Centenarian results were compared with published birth cohort-matched results. Data from offspring and reference cohorts were analyzed to determine differences in oral health and associations between oral health measures and specific medical conditions. RESULTS: The edentulous rate of centenarians (36.5%) was lower than that of their birth cohort (46%) when they were aged 65 to 74 in 1971 to 1974 (according to National Center of Health Statistics). Adjusting for confounding factors, the reference cohort was more likely to be edentulous (adjusted odds ratio (AOR) = 2.78, 95% confidence interval CI = 1.17-6.56), less likely to have all or more than half of their own teeth (AOR = 0.48, 95% CI = 0.3-0.76), and less likely to report excellent or very good oral health (AOR = 0.65, 95% CI = 0.45-0.94) than the centenarian offspring. CONCLUSION: Centenarians and their offspring have better oral health than their respective birth cohorts. Oral health may prove to be a helpful marker for systemic health and healthy aging.

Incident comorbidities and all-cause mortality among 5-year survivors of Stage I and II breast cancer diagnosed at age 65 or older: a prospective-matched cohort study.

Five-year breast cancer survivors, diagnosed after 65 years of age, may develop more incident comorbidities than similar populations free of cancer. We investigated whether 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 whether incident comorbidities are associated with all-cause mortality. In this prospective cohort study, 1,361 older 5-year early-stage breast cancer survivors diagnosed between 1990 and 1994 and 1,361 age- and health system-matched women were followed for 10 years. Adjudicated medical record review captured prevalent and incident comorbidities during follow-up or until death as collected from the National Death Index. Older 5-year breast cancer survivors did not acquire incident comorbidities more often than matched women free of breast cancer in the subsequent 10 years [hazard ratio (HR) 1.0, 95 % confidence interval (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.

Cognitive impairment in older patients with breast cancer before systemic therapy: is there an interaction between cancer and comorbidity?

PURPOSE: To determine if older patients with breast cancer have cognitive impairment before systemic therapy. PATIENTS AND METHODS: Participants were patients with newly diagnosed nonmetastatic breast cancer and matched friend or community controls age > 60 years without prior systemic treatment, dementia, or neurologic disease. Participants completed surveys and a 55-minute battery of 17 neuropsychological tests. Biospecimens were obtained for APOE genotyping, and clinical data were abstracted. Neuropsychological test scores were standardized using control means and standard deviations (SDs) and grouped into five domain z scores. Cognitive impairment was defined as any domain z score two SDs below or ≥ two z scores 1.5 SDs below the control mean. Multivariable analyses evaluated pretreatment differences considering age, race, education, and site; comparisons between patient cases also controlled for surgery. RESULTS: The 164 patient cases and 182 controls had similar neuropsychological domain scores. However, among patient cases, those with stage II to III cancers had lower executive function compared with those with stage 0 to I disease, after adjustment (P = .05). The odds of impairment were significantly higher among older, nonwhite, less educated women and those with greater comorbidity, after adjustment. Patient case or control status, anxiety, depression, fatigue, and surgery were not associated with impairment. However, there was an interaction between comorbidity and patient case or control status; comorbidity was strongly associated with impairment among patient cases (adjusted odds ratio, 8.77; 95% CI, 2.06 to 37.4; P = .003) but not among controls (P = .97). Only diabetes and cardiovascular disease were associated with impairment among patient cases. CONCLUSION: There were no overall differences between patients with breast cancer and controls before systemic treatment, but there may be pretreatment cognitive impairment within subgroups of patient cases with greater tumor or comorbidity burden.

Older women's experience with breast cancer treatment decisions.

The purpose of this study was to better understand older women's experience with breast cancer treatment decisions. We conducted a longitudinal study of non-demented, English-speaking women ≥ 65 years recruited from three Boston-based breast imaging centers. We interviewed women at the time of breast biopsy (before they knew their results) and 6 months later. At baseline, we assessed intention to accept different breast cancer treatments, sociodemographic, and health characteristics. At follow-up, we asked women about their involvement in treatment decisions, to describe how they chose a treatment, and influencing factors. We assessed tumor characteristics through chart abstraction. We used quantitative and qualitative analyses. Seventy women (43 ≥ 75 years) completed both interviews and were diagnosed with breast cancer; 91 % were non-Hispanic white. At baseline, women 75+ were less likely than women 65-74 to report that they would accept surgery and/or take a medication for ≥ 5 years if recommended for breast disease. Women 75+ were ultimately less likely to receive hormonal therapy for estrogen receptor positive tumors than women 65-74. Women 75+ asked their surgeons fewer questions about their treatment options and were less likely to seek information from other sources. A surgeon's recommendation was the most influential factor affecting older women's treatment decisions. In open-ended comments, 17 women reported having no perceived choice about treatment and 42 stated they simply followed their physician's recommendation for at least one treatment choice. In conclusion, to improve care of older women with breast cancer, interventions are needed to increase their engagement in treatment decision-making.