Zhigang Duan

Congestive Heart Failure in Older Women Treated With Adjuvant Anthracycline Chemotherapy for Breast Cancer

PURPOSE Limited data are available on long-term cardiac safety of adjuvant anthracycline chemotherapy in breast cancer patients over age 65 years. We evaluated rates and predictors of congestive heart failure (CHF) in this population. PATIENTS AND METHODS We used the Surveillance, Epidemiology, and End Results Medicare database and included women with no history of CHF who were age 66 to 80 years and diagnosed with stage I to III breast cancer from 1992 to 2002. Cumulative rates of CHF were estimated, and multivariable Cox regression analysis was used to determine factors associated with the development of CHF. RESULTS A total of 43,338 women were included. Anthracycline-treated women were younger, with fewer comorbidities and more advanced disease than women who received nonanthracycline or no chemotherapy (P < .001 for each). The adjusted hazard ratio (HR) for CHF was 1.26 (95% CI, 1.12 to 1.42) for women aged 66 to 70 treated with anthracycline compared with other chemotherapy. For women aged 71 to 80, adjuvant chemotherapy type was not associated with CHF. The following baseline characteristics were significant predictors of CHF: age (HR, 1.79 per 10 years; 95% CI, 1.66 to 1.93), black race (HR, 1.40; 95% CI, 1.30 to 1.50), trastuzumab treatment (HR, 1.46; 95% CI, 1.21 to 1.77), hypertension (HR, 1.45; 95% CI, 1.39 to 1.52), diabetes (HR, 1.74; 95% CI, 1.66 to 1.83), and coronary artery disease (HR, 1.58; 95% CI, 1.39 to 1.79). Left-sided radiotherapy did not confer an elevated risk of CHF (HR, 1.04; 95% CI, 0.98 to 1.11). CONCLUSION Women aged 66 to 70 years who received adjuvant anthracyclines had significantly higher rates of CHF. The difference in rates of CHF continued to increase through more than 10 years of follow-up.

Use and outcomes of adjuvant chemotherapy in older women with breast cancer

PURPOSE This study was undertaken to determine patterns and outcomes of adjuvant chemotherapy use in a population-based cohort of older women with primary breast cancer. PATIENTS AND METHODS Women were identified from the Surveillance, Epidemiology, and End Results-Medicare-linked database who met the following criteria: age > or = 65 years, stage I to III breast cancer, and diagnosis between 1991 and 1999. Adjuvant chemotherapy use was ascertained by Common Procedural Terminology J codes. Logistic regression analysis was performed to determine factors associated with chemotherapy use. Multivariate Cox proportional hazards models were used to calculate the hazard of death for women with and without chemotherapy. RESULTS A total of 41,390 women met study criteria, of whom 4,500 (10.9%) received chemotherapy. The use of adjuvant chemotherapy more than doubled during the 1990s, from 7.4% in 1991 to 16.3% in 1999 (P < .0001), with a significant shift toward anthracycline use. Women who were younger, white, with lower comorbidity scores, more advanced stage disease, and estrogen receptor (ER) -negative disease were significantly more likely to receive chemotherapy. Chemotherapy was not associated with improved survival among women with lymph node-negative (LN) disease or LN-positive, ER-positive disease (hazard ratio [HR], 1.05; 95% CI, 0.85 to 1.31). However, among women with LN-positive, ER-negative breast cancer, chemotherapy was associated with a significant reduction in breast cancer mortality (HR, 0.72; 95% CI, 0.54 to 0.96). A similar significant benefit of chemotherapy was seen in the subset of women age 70 years or older (HR, 0.74; 95% CI, 0.56 to 0.97). CONCLUSION In this observational cohort, chemotherapy was associated with a significant reduction in mortality among older women with ER-negative, LN-positive breast cancer.

Limits of observational data in determining outcomes from cancer therapy

Observational data are used increasingly to assess the effectiveness of therapies. However, selection biases are likely to have an impact on results and threaten the validity of these studies.

Squamous Cell Carcinoma of the Breast

PURPOSE Squamous cell carcinoma (SCC) of the breast is rare and generally aggressive. In this study, we analyzed 33 patients treated at The University of Texas M.D. Anderson Cancer Center (Houston, TX) and a series of 137 patients identified through the Surveillance, Epidemiology, and End Results (SEER) database to make therapy recommendations. METHODS Records of The University of Texas M.D. Anderson Cancer Center were searched for patients diagnosed with breast SCC from 1985 to 2001. All biopsy material was reviewed by a dedicated breast pathologist who performed immunohistochemistry for hormone receptors and the epidermal growth factor receptor (EGFR). We searched the SEER database for patients with breast SCC diagnosed between 1988 and 2001. RESULTS We identified 33 patients with breast SCC, of whom two patients had metastatic disease at diagnosis. The median relapse-free survival (RFS) of 31 patients with localized disease was 20 months (range, 1 to 108 months), with a 26% RFS rate at 5 years. The median overall survival in these patients was 37 months (range, 12 to 108 months), with 40% surviving at 5 years. Median survival from the time recurrent disease was recognized was 14 months (range, 2 to 86 months). Tumors were usually hormone receptor-and HER2/neu-negative, though EGFR was frequently overexpressed. Information from the SEER database was consistent with most of our findings. CONCLUSION SCC of the breast is aggressive and often treatment-refractory. The role of platinum salts, EGFR inhibitors, and other novel agents needs to be explored.

Acute Myeloid Leukemia After Adjuvant Breast Cancer Therapy in Older Women: Understanding Risk

PURPOSE The purpose of this study was to determine the risk of developing acute myeloid leukemia (AML) after adjuvant chemotherapy for breast cancer in older women. PATIENTS AND METHODS Data from the Surveillance, Epidemiology, and End Results-Medicare linked database were used for women diagnosed with nonmetastatic breast cancer from 1992 to 2002. The primary end point was a claim with an inpatient or outpatient diagnosis of AML (International Classification of Diseases ninth revision, codes 205 to 208), comparing patients treated with and without adjuvant chemotherapy, and by differing chemotherapy regimens. The cumulative hazard of AML was estimated using the Kaplan-Meier method. Cox proportional hazards models were used to determine factors independently associated with the development of AML. RESULTS In this observational study, there were 64,715 patients: 10,130 received adjuvant chemotherapy and 54,585 did not. The median patient age was 75.6 years (range, 66 to 104 years). The mean follow-up was 54.8 months (range, 13 to 144 months). The absolute risk of developing AML at 10 years after any adjuvant chemotherapy for breast cancer was 1.8% versus 1.2% for women who had not received chemotherapy. The adjusted hazard ratio for AML with adjuvant chemotherapy versus none was 1.53 (95% CI, 1.14 to 2.06). Granulocyte colony-stimulating factor (G-CSF) within the first year of diagnosis did not convey a significantly increased risk of AML (hazard ratio, 1.14; 95% CI, 0.67 to 1.92). CONCLUSION There is a small but real increase in AML after adjuvant chemotherapy for breast cancer in older women. This study may underestimate the true incidence because myelodysplastic syndrome cannot be identified through claims. G-CSF use within the first year of diagnosis does not convey an increased risk of AML in older women.

Radiation Use and Long-Term Survival in Breast Cancer Patients With T1, T2 Primary Tumors and One to Three Positive Axillary Lymph Nodes

BACKGROUND For patients with Stage II breast cancer with one to three positive lymph nodes, controversy exists about whether radiation as a component of treatment provides a survival benefit. METHODS AND MATERIALS We analyzed data from patients with Stage II breast cancer with one to three positive lymph nodes diagnosed from 1988-2002 in the Surveillance, Epidemiology, and End Results registry and compared the outcome of 12,693 patients treated with breast-conservation therapy with radiation (BCT + XRT) with the 18,902 patients treated with mastectomy without radiation (MRM w/o XRT). RESULTS Patients treated with BCT + XRT were younger, were more likely to be treated in recent years of the study period, more commonly had T1 primary tumors, and had fewer involved nodes compared with those treated with MRM w/o XRT (p < 0.001 for all differences). The 15-year breast cancer-specific survival rate for the BCT + XRT group was 80% vs. 72% for the MRM w/o XRT group (p < 0.001). Cox regression analysis showed that MRM w/o XRT was associated with a hazard ratio for breast cancer death of 1.19 (p < 0.001) and for overall death of 1.25 (p < 0.001). The survival benefit in the BCT + XRT group was not limited to subgroups with high-risk disease features. CONCLUSIONS Radiation use was independently associated with improved survival for patients with Stage II breast cancer with one to three positive lymph nodes. Because multivariate analyses of retrospective data cannot account for all potential biases, these data require confirmation in randomized clinical trials.

The Effect of HIV Viral Control on the Incidence of Hepatocellular Carcinoma in Veterans with Hepatitis C and HIV Coinfection

Background:HIV increases the risk of progression to hepatic fibrosis and cirrhosis among individuals coinfected with hepatitis C virus (HCV). However, the impact of HIV-related immune suppression on the risk of hepatocellular carcinoma (HCC) is currently unknown. Methods:We used the Veterans Affairs HIV Clinical Case Registry to identify patients with HIV infection between 1985 and 2010 and HCV coinfection (positive HCV RNA or genotype test) between 1995 and 2010. The outcome was incident HCC as indicated by International Classification of Diseases, 9th revision, Clinical Modification code (87% positive predictive value). Patients with HCV monoinfection were included as a comparison group for HCC incidence. Age-adjusted HCC incidence rates were calculated for the coinfected cohort and HCV monoinfected cohort. Cox proportional hazard models were used to determine hazard ratios (HRs) and 95% confidence intervals (CIs) for each risk factor on the time to HCC diagnosis in the coinfected cohort. Results:There were 66,991 veterans with HIV; 8563 had at least 1 positive HCV RNA test, and 234 of these developed HCC. The overall age-adjusted incidence rate of HCC in monoinfected patients was 2.99/1000 person-years vs. 4.44/1000 person-years in coinfected patients. In patients with coinfection, presence of cirrhosis (HR = 4.88; 95% CI: 3.30 to 7.21), HIV diagnosis >2002 (HR = 4.65; 95% CI: 2.70 to 8.02), and a recent low CD4+ cell count <200 (HR = 1.71; 95% CI: 1.20 to 2.45) were associated with an increased risk for HCC. Conclusions:The risk of HCC in HCV- and HIV-coinfected veteran men was higher than HCV monoinfection. Diagnosis of cirrhosis and low recent CD4+ cell count were the most important predictors of developing HCC in this group.

Use of Intravenous Bisphosphonates in Older Women with Breast Cancer

INTRODUCTION i.v. bisphosphonates reduce skeletal events in women with bone metastases from breast cancer, but little is known about the prevalence and duration of bisphosphonate use. METHODS Patients were identified from the Surveillance, Epidemiology, and End Results-Medicare database who were aged > or =65 years and were diagnosed with invasive breast cancer in 1995-2002. Healthcare Common Procedure Coding System codes were used to identify patients treated with pamidronate and zoledronic acid. Descriptive statistics were used to describe patterns of use. Multivariate analyses were performed to determine the predictors of bisphosphonate use. RESULTS In total, 55,864 women with breast cancer were included, with 307,467 person-years of follow-up. Overall, 1.26% of women with all stages of breast cancer received i.v. bisphosphonates. In 2004, 2% of all breast cancer patients and 32% of patients with distant stage disease received bisphosphonates. Approximately two thirds of patients treated with bisphosphonates received zoledronic acid and one third received pamidronate in 2004. Multivariate analyses showed that patients who were > or =75 years old were less likely to receive bisphosphonates (75-79 years versus 65-69 years: odds ratio [OR], 0.81; 95% confidence interval [CI], 0.70-0.93; 80+ years versus 65-69 years: OR, 0.49; 95% CI, 0.42-0.57). The use of bisphosphonates dramatically increased over time. The majority of living patients were continued on i.v. bisphosphonates once started (83% at 1 year, 64% at 3 years, 50% at 5 years), but the median survival time after initiation of i.v. bisphosphonates was only 21 months. CONCLUSIONS i.v. bisphosphonates appear to be underused in patients with metastatic breast cancer, particularly among those patients >75 years of age.

Risk of Upper Gastrointestinal Cancers in Patients With Gastroesophageal Reflux Disease After a Negative Screening Endoscopy

BACKGROUND & AIMS Practice guidelines recommend a 1-time screening endoscopy for patients with gastroesophageal reflux disease (GERD) who are at high risk for Barretts esophagus or malignancy. However, little is known about the risk of cancer in patients with negative findings from screening endoscopies. METHODS We conducted a retrospective cohort study using data from 121 Veterans Health Administration facilities nationwide to determine the incidence rate of esophageal adenocarcinoma (EA) separately, as well as any upper gastrointestinal cancers, in patients with an initial negative screening endoscopy (esophagogastroduodenoscopy [EGD]). We included veteran patients with GERD diagnosed between 2004 and 2009 who had a negative screening EGD within 1 year of diagnosis. We estimated the incidence rate of EA, and any upper gastrointestinal cancer, in patients with GERD who had a negative screening EGD. We examined differences in demographic, clinical, and facility factors among patients with and without cancer. RESULTS We identified 68,610 patients with GERD and a negative screening EGD (mean age, 55.5 y; 90% men; 67.5% white). During a mean follow-up period of 3.2 years, 10 patients developed EA and 29 patients developed any upper gastrointestinal malignancies, including EA. The incidence of subsequent EA in this group was 4.6/100,000 patient-years of follow-up evaluation, whereas the incidence of any upper gastrointestinal cancers was 13.2/100,000 patient-years of follow-up evaluation. Patients with a subsequent cancer were significantly older and had higher comorbidity scores than patients without cancer. Other clinical and facility factors did not differ significantly between these 2 groups. CONCLUSIONS The risk of cancer is low, over a mean 3-year period, for patients with GERD who had a negative screening endoscopy. These findings justify recommendations for a 1-time screening endoscopy for patients with GERD.

Risk of hospitalisation after primary treatment for prostate cancer.

To compare the risk of hospitalisation and associated costs in patients after treatment for prostate cancer.