Erin J. Aiello Bowles

Variability in Reexcision Following Breast Conservation Surgery

CONTEXT Health care reform calls for increasing physician accountability and transparency of outcomes. Partial mastectomy is the most commonly performed procedure for invasive breast cancer and often requires reexcision. Variability in reexcision might be reflective of the quality of care. OBJECTIVE To assess hospital and surgeon-specific variation in reexcision rates following partial mastectomy. DESIGN, SETTING, AND PATIENTS An observational study of breast surgery performed between 2003 and 2008 intended to evaluate variability in breast cancer surgical care outcomes and evaluate potential quality measures of breast cancer surgery. Women with invasive breast cancer undergoing partial mastectomy from 4 institutions were studied (1 university hospital [University of Vermont] and 3 large health plans [Kaiser Permanente Colorado, Group Health, and Marshfield Clinic]). Data were obtained from electronic medical records and chart abstraction of surgical, pathology, radiology, and outpatient records, including detailed surgical margin status. Logistic regression including surgeon-level random effects was used to identify predictors of reexcision. MAIN OUTCOME MEASURE Incidence of reexcision. RESULTS A total of 2206 women with 2220 invasive breast cancers underwent partial mastectomy and 509 patients (22.9%; 95% CI, 21.2%-24.7%) underwent reexcision (454 patients [89.2%; 95% CI, 86.5%-91.9%] had 1 reexcision, 48 [9.4%; 95% CI, 6.9%-12.0%] had 2 reexcisions, and 7 [1.4%; 95% CI, 0.4%-2.4%] had 3 reexcisions). Among all patients undergoing initial partial mastectomy, total mastectomy was performed in 190 patients (8.5%; 95% CI, 7.2%-9.5%). Reexcision rates for margin status following initial surgery were 85.9% (95% CI, 82.0%-89.8%) for initial positive margins, 47.9% (95% CI, 42.0%-53.9%) for less than 1.0 mm margins, 20.2% (95% CI, 15.3%-25.0%) for 1.0 to 1.9 mm margins, and 6.3% (95% CI, 3.2%-9.3%) for 2.0 to 2.9 mm margins. For patients with negative margins, reexcision rates varied widely among surgeons (range, 0%-70%; P = .003) and institutions (range, 1.7%-20.9%; P < .001). Reexcision rates were not associated with surgeon procedure volume after adjusting for case mix (P = .92). CONCLUSION Substantial surgeon and institutional variation were observed in reexcision following partial mastectomy in women with invasive breast cancer.

Risk of Heart Failure in Breast Cancer Patients After Anthracycline and Trastuzumab Treatment: A Retrospective Cohort Study

Background Clinical trials demonstrated that women treated for breast cancer with anthracycline or trastuzumab are at increased risk for heart failure and/or cardiomyopathy (HF/CM), but the generalizability of these findings is unknown. We estimated real-world adjuvant anthracycline and trastuzumab use and their associations with incident HF/CM. Methods We conducted a population-based, retrospective cohort study of 12 500 women diagnosed with incident, invasive breast cancer from January 1, 1999 through December 31, 2007, at eight integrated Cancer Research Network health systems. Using administrative procedure and pharmacy codes, we identified anthracycline, trastuzumab, and other chemotherapy use. We identified incident HF/CM following chemotherapy initiation and assessed risk of HF/CM with time-varying chemotherapy exposures vs no chemotherapy. Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for age at diagnosis, stage, Cancer Research Network site, year of diagnosis, radiation therapy, and comorbidities. Results Among 12 500 women (mean age = 60 years, range = 22–99 years), 29.6% received anthracycline alone, 0.9% received trastuzumab alone, 3.5% received anthracycline plus trastuzumab, 19.5% received other chemotherapy, and 46.5% received no chemotherapy. Anthracycline and trastuzumab recipients were younger, with fewer comorbidities than recipients of other chemotherapy or none. Compared with no chemotherapy, the risk of HF/CM was higher in patients treated with anthracycline alone (adjusted HR = 1.40, 95% CI = 1.11 to 1.76), although the increased risk was similar to other chemotherapy (adjusted HR = 1.49, 95% CI = 1.25 to 1.77); the risk was highly increased in patients treated with trastuzumab alone (adjusted HR = 4.12, 95% CI = 2.30 to 7.42) or anthracycline plus trastuzumab (adjusted HR = 7.19, 95% CI = 5.00 to 10.35). Conclusions Anthracycline and trastuzumab were primarily used in younger, healthier women and associated with increased HF/CM risk compared with no chemotherapy. This population-based observational study complements findings from clinical trials on cancer treatment safety.

Understanding high-quality cancer care: a summary of expert perspectives.

The Institute of Medicine (IOM) report Crossing the Quality Chasm proposed 6 aims for high‐quality healthcare: effective, safe, timely, efficient, equitable, and patient‐centered, and emphasized care coordination. Through interviews with nationally recognized experts in healthcare quality, perspectives on barriers and facilitators to achieving these aims for cancer patients were elicited.

Nurse Navigators in Early Cancer Care: A Randomized, Controlled Trial

PURPOSE To determine whether a nurse navigator intervention improves quality of life and patient experience with care for people recently given a diagnosis of breast, colorectal, or lung cancer. PATIENTS AND METHODS Adults with recently diagnosed primary breast, colorectal, or lung cancer (n = 251) received either enhanced usual care (n = 118) or nurse navigator support for 4 months (n = 133) in a two-group cluster randomized, controlled trial with primary care physicians as the units of randomization. Patient-reported measures included the Functional Assessment of Cancer Therapy-General (FACT-G) Quality of Life scale, three subscales of the Patient Assessment of Chronic Illness Care (PACIC), and selected subscales from a cancer adaptation of the Picker Institutes patient experience survey. Self-report measures were collected at baseline, 4 months, and 12 months. Automated administrative data were used to assess time to treatment and total health care costs. RESULTS There were no significant differences between groups in FACT-G scores. Nurse navigator patients reported significantly higher scores on the PACIC and reported significantly fewer problems with care, especially psychosocial care, care coordination, and information, as measured by the Picker instrument. Cumulative costs after diagnosis did not differ significantly between groups, but lung cancer costs were

Defining menopausal status in epidemiologic studies: A comparison of multiple approaches and their effects on breast cancer rates

6,852 less among nurse navigator patients. CONCLUSION Compared with enhanced usual care, nurse navigator support for patients with cancer early in their course improves patient experience and reduces problems in care, but did not differentially affect quality of life.

Circulating serum xenoestrogens and mammographic breast density.

OBJECTIVES Menopausal status is a common covariate in epidemiologic studies. Still, there are no standard definitions for menopausal status using observational data. This study assesses distinctions between menopausal status definitions using commonly collected epidemiologic data, and explores their impact on study outcomes using breast cancer rates as an example. STUDY DESIGN Using survey data from 227,700 women aged 40-64 who received screening mammograms from the Breast Cancer Surveillance Consortium, we classified menopausal status under five different definitions: one complex definition combining multiple variables, two definitions using age as a proxy for menopausal status, one based only on menstrual period status, and one based on age and menstrual period status. MAIN OUTCOME MEASURES We compared the distribution of menopausal status and menopausal status-specific breast cancer incidence and detection rates across definitions for menopausal status. RESULTS Overall, 36% and 29% of women were consistently classified as postmenopausal and premenopausal, respectively, across all definitions. Menopausal status-specific breast cancer incidence and detection rates were similar across definitions. Rates were unchanged when information regarding natural menopause, bilateral oophorectomy, hormone therapy, and timing of last menstrual period were sequentially added to definitions of postmenopausal status. CONCLUSIONS Distinctions in menopausal status definitions contribute to notable differences in how women are classified, but translate to only slight differences in menopausal status-specific breast cancer rates.

Sources of cadmium exposure among healthy premenopausal women

IntroductionHumans are widely exposed to estrogenically active phthalates, parabens, and phenols, raising concerns about potential effects on breast tissue and breast cancer risk. We sought to determine the association of circulating serum levels of these chemicals (reflecting recent exposure) with mammographic breast density (a marker of breast cancer risk).MethodsWe recruited postmenopausal women aged 55 to 70 years from mammography clinics in Madison, Wisconsin (N = 264). Subjects completed a questionnaire and provided a blood sample that was analyzed for mono-ethyl phthalate, mono-butyl phthalate, mono-benzyl phthalate, butyl paraben, propyl paraben, octylphenol, nonylphenol, and bisphenol A (BPA). Percentage breast density was measured from mammograms by using a computer-assisted thresholding method.ResultsSerum BPA was positively associated with mammographic breast density after adjusting for age, body mass index, and other potentially confounding factors. Mean percentage density was 12.6% (95% confidence interval (CI), 11.4 to 14.0) among the 193 women with nondetectable BPA levels, 13.7% (95% CI, 10.7 to 17.1) among the 35 women with detectable levels below the median (<0.55 ng/ml), and 17.6% (95% CI, 14.1 to 21.5) among the 34 women with detectable levels above the median (>0.55 ng/ml; Ptrend = 0.01). Percentage breast density was also elevated (18.2%; 95% CI, 13.4 to 23.7) among the 18 women with serum mono-ethyl phthalate above the median detected level (>3.77 ng/ml) compared with women with nondetectable BPA levels (13.1%; 95% CI, 11.9 to 14.3; Ptrend = 0.07). No other chemicals demonstrated associations with percentage breast density.ConclusionsPostmenopausal women with high serum levels of BPA and mono-ethyl phthalate had elevated breast density. Further investigation of the impact of BPA and mono-ethyl phthalate on breast cancer risk by using repeated serum measurements or other markers of xenoestrogen exposure are needed.

Outpatient Use of Low Molecular Weight Heparin Monotherapy for First-Line Treatment of Venous Thromboembolism in Advanced Cancer

BACKGROUND Cadmium, a persistent and widespread environmental pollutant, has been associated with kidney function impairment and several diseases. Cigarettes are the dominant source of cadmium exposure among smokers; the primary source of cadmium in non-smokers is food. We investigated sources of cadmium exposure in a sample of healthy women. METHODS In a cross-sectional study, 191 premenopausal women completed a health questionnaire and a food frequency questionnaire. The cadmium content of spot urine samples was measured with inductively-coupled plasma mass spectrometry and normalized to urine creatinine content. Multivariable linear regression was used to estimate the strength of association between smoking habits and, among non-smokers, usual foods consumed and urinary cadmium, adjusted for age, race, multivitamin and supplement use, education, estimated total energy intake, and parity. RESULTS Geometric mean urine creatinine-normalized cadmium concentration (uCd) of women with any history of cigarette smoking was 0.43 μg/g (95% confidence interval (CI): 0.38-0.48 μg/g) and 0.30 μg/g (0.27-0.33 μg/g) among never-smokers, and increased with pack-years of smoking. Analysis of dietary data among women with no reported history of smoking suggested that regular consumption of eggs, hot cereals, organ meats, tofu, vegetable soups, leafy greens, green salad, and yams was associated with uCd. Consumption of tofu products showed the most robust association with uCd; each weekly serving of tofu was associated with a 22% (95% CI: 11-33%) increase in uCd. Thus, uCd was estimated to be 0.11 μg/g (95% CI: 0.06-0.15 μg/g) higher among women who consumed any tofu than among those who consumed none. CONCLUSIONS Cigarette smoking is likely the most important source of cadmium exposure among smokers. Among non-smokers, consumption of specific foods, notably tofu, is associated with increased urine cadmium concentration.

Patterns and Predictors of First-line Chemotherapy Use among Adults with Advanced Non-small Cell Lung Cancer in the Cancer Research Network

BACKGROUND Evidence-based treatment guidelines recommend low molecular weight heparin (LMWH) monotherapy for cancer-associated venous thromboembolism (VTE). This analysis assessed the first-line treatment strategies for VTE in patients with advanced solid tumors. METHODS Using administrative data from advanced lung, prostate, colon, or breast cancer patients diagnosed between January 2000 and December 2007 at four HMOs with integrated delivery systems, patients with an inpatient or outpatient VTE diagnosed within 2 years after cancer diagnosis and an outpatient purchase of warfarin, LMWH, and/or fondaparinux anticoagulant within 7 days of the VTE diagnosis were identified. First-line outpatient VTE pharmacological treatment and factors independently associated with receipt/non-receipt of LMWH monotherapy were assessed. RESULTS Overall, 25% of the 1,089 eligible patients received LMWH monotherapy as primary VTE treatment. The percentage increased steadily over time from 18% among patients diagnosed in 2000 to 31% among those diagnosed in 2007. Factors associated with LMWH monotherapy included VTE diagnosis year, chemotherapy within 60 days prior to VTE diagnosis, history of VTE prior to cancer diagnosis, and invasive surgery in the 90 days following VTE diagnosis. Colorectal and prostate cancer patients versus lung cancer patients and stage III versus stage IV patients were less likely to be treated with LMWH monotherapy. CONCLUSIONS Adoption of LMWH monotherapy as initial treatment for cancer-associated VTE was low but increased steadily over the study period. Future studies should explore reasons underlying the underutilization of this preferred evidence-based treatment as well as the comparative effectiveness of LMWH versus warfarin-based anticoagulation in real-world cancer patients with VTE.

Prognostic Significance of Mammographic Density Change After Initiation of Tamoxifen for ER-Positive Breast Cancer

BACKGROUND Relatively low rates of chemotherapy receipt have been observed in older patients diagnosed with advanced non-small cell lung cancer (NSCLC) in SEER-Medicare-based studies. However, little is known about variation in first-line NSCLC chemotherapy use in younger patients, health maintenance organization (HMO)-based settings, and for high-cost, novel agents, such as bevacizumab and erlotinib. METHODS A cohort of 6614 stage IIIB/IV NSCLC patients aged ≥ 21 years diagnosed between 2000 and 2007 was identified at four HMOs that participate in the Cancer Research Network (CRN). Demographic, comorbidity, tumor characteristics, and chemotherapy treatment data were included in logistic regression models to identify factors associated with chemotherapy receipt and tests of association examined secular and age-specific variation in first-line chemotherapy regimens. RESULTS Within 120 days of diagnosis, 3612 (55%) patients received chemotherapy; increasing from 52% of patients diagnosed in 2000 to 59% in 2007 (p<0.001). Receipt was significantly higher for patients aged <65 years (64% versus 46% in ≥ 65) and was inversely related to stage and comorbidites (all p<0.001). Carboplatin and paclitaxel were received most frequently. Erlotinib and bevacizumab use in the later years of the study was associated with a significant change in distributions of first-line chemotherapies (p<0.001). CONCLUSIONS For patients alive 30 days post diagnosis, chemotherapy use was higher in the aged population (>65 years) than previously published estimates, and higher still among younger patients. Chemotherapy use increased over the observation period, and the mix of first-line therapies used changed substantially over time. Of note, novel, high cost treatments were used in first-line therapy prior to FDA approval, increasing significantly throughout the study period. These findings demonstrate the utility of HMO CRN data to augment SEER-Medicare to conduct comparative effectiveness research related to chemotherapy use and the use of specific agents, especially among younger patients.