Biomedical subjects

Andrea Troxel

Publications and source records attributed to Andrea Troxel.

12 recordsLinked to original sources

PubMed2006

Pseudo-likelihood methods for longitudinal binary data with non-ignorable missing responses and covariates.

In this paper we consider longitudinal studies in which the outcome to be measured over time is binary, and the covariates of interest are categorical. In longitudinal studies it is common for the outcomes and any time-varying covariates to be missing due to missed study visits, resulting in non-monotone patterns of missingness. Moreover, the reasons for missed visits may be related to the specific values of the response and/or covariates that should have been obtained, i.e. missingness is non-ignorable. With non-monotone non-ignorable missing response and covariate data, a full likelihood approach is quite complicated, and maximum likelihood estimation can be computationally prohibitive when there are many occasions of follow-up. Furthermore, the full likelihood must be correctly specified to obtain consistent parameter estimates. We propose a pseudo-likelihood method for jointly estimating the covariate effects on the marginal probabilities of the outcomes and the parameters of the missing data mechanism. The pseudo-likelihood requires specification of the marginal distributions of the missingness indicator, outcome, and possibly missing covariates at each occasions, but avoids making assumptions about the joint distribution of the data at two or more occasions. Thus, the proposed method can be considered semi-parametric. The proposed method is an extension of the pseudo-likelihood approach in Troxel et al. to handle binary responses and possibly missing time-varying covariates. The method is illustrated using data from the Six Cities study, a longitudinal study of the health effects of air pollution.

Air Pollutants↗

PubMed2004

Men with breast cancer have better disease-specific survival than women.

HYPOTHESIS: Male breast cancer patients have better disease-specific survival than carefully matched female breast cancer patients. DESIGN: Retrospective study. SETTING: University hospital. PATIENTS AND METHODS: Each man in the breast cancer database at Columbia-Presbyterian Medical Center (New York, NY) between the years 1980 and 1998 was matched with a woman. Matching was done based on age and date of diagnosis, stage, and primary histologic findings. MAIN OUTCOME MEASURES: The overall survivals and disease-specific survivals of the male breast cancer group and female breast cancer group were compared. RESULTS: Fifty-three male patients were matched with an equal number of female breast cancer patients. The Kaplan-Meier curves demonstrated that there was no significant difference in overall survival. The 5- and 10-year survivals for women were 0.77 and 0.51, and for men 0.77 and 0.56. When the Kaplan-Meier curves for breast cancer-specific survival were compared, however, there was a significant difference in the 5- and 10-year survivals (P = .05, log-rank test). For women, the 5- and 10-year disease-specific survival was 0.81 and 0.7, respectively, while for men it was 0.9 and 0.9, respectively. In a Cox regression analysis for time to death from breast cancer, stage was the only predictor of death that approached significance (P = .06). CONCLUSIONS: While the overall survivals were equivalent, male breast cancer patients had significantly better disease-specific survivals compared with their female counterparts. Male patients were 4 times more likely to die of other causes than their breast cancer.

Aged↗

PubMed2004

Predictors of nonsentinel node metastasis in patients with breast cancer after sentinel node metastasis.

HYPOTHESIS: The presence of nonsentinel lymph node (NSLN) metastasis after having a positive sentinel lymph node dissection finding is associated with tumor size and stage, the presence of lymphovascular invasion, micrometastasis, and extranodal extension. DESIGN: Retrospective case series. SETTING: University hospital. PATIENTS: Four hundred seven consecutive patients at a single institution who underwent sentinel lymph node dissection as part of breast conservation or mastectomy with biopsy-proved cancer. INTERVENTION: Completion axillary lymph node dissection and definitive therapy. MAIN OUTCOME MEASURES: Sentinel node metastasis, NSLN metastasis, tumor size and stage, lymphovacular invasion, micrometastasis, extronodal extension, histological tumor characteristics, and number of sentinel nodes removed. RESULTS: In a univariate analysis, size of the primary tumor and extranodal extension were associated with having positive NSLN findings. The presence of micrometastasis was associated with negative NSLN findings. When all factors were included in a logistic regression analysis, the significant predictor of NSLN metastasis was extranodal extension (P =.002). Lymphovascular invasion was not associated with positive NSLN findings (P =.11). The number of sentinel nodes removed also had no bearing on the status of the NSLNs (P =.37). CONCLUSIONS: Although primary tumor size and micrometastases correlate with the status of the NSLNs, extranodal extension is the most important independent predictor of NSLN metastasis. These findings may ultimately spare patients a full axillary lymph node dissection. However, pending results of larger clinical trials, full axillary lymph node dissection is still recommended for patients with sentinel lymph node metastases.

Adult↗

PubMed2004

Pure mucinous carcinoma of the breast.

BACKGROUND: The lack of a standard definition of "pure" mucinous carcinoma of the breast has made it difficult to compare data from different studies. This study used the most stringent criteria to define parameters for truly pure lesions. METHODS: Sixty-five patients were identified. The database was used to evaluate patients' demographics, tumor characteristics, and outcomes. Survival curves and predictors of survival were analyzed. RESULTS: The mean age of presentation was 67 years. The majority (96%) of patients presented with early-stage disease. The 5- and 10-year overall survival rates were 93.6% and 72.8%, respectively. The number of involved axillary lymph nodes was the only significant predictor of death (P = 0.02). CONCLUSIONS: Pure mucinous carcinoma of the breast has a favorable prognosis. Tumor size does not appear to impact survival, perhaps because the volume of mucin overestimates tumor burden. The number of involved axillary lymph nodes was the only significant predictor of death from disease.

Adenocarcinoma, Mucinous↗

PubMed2004

Cardiac toxicity observed in association with high-dose cyclophosphamide-based chemotherapy for metastatic breast cancer.

INTRODUCTION: Cyclophosphamide is an alkylating agent given frequently as a component of many conditioning regimens. In high doses, its nonhematological dose-limiting toxicity is cardiomyopathy. STUDY DESIGN: We combined paclitaxel, melphalan and high-dose cyclophosphamide, thiotepa, and carboplatin in a triple sequential high-dose regimen for patients with metastatic breast cancer. Analysis was performed on 61 women with chemotherapy-responsive metastatic breast cancer receiving 96-h infusional cyclophosphamide as part of a triple sequential high-dose regimen to assess association between presence of peritransplant congestive heart failure (CHF) and the following pretreatment characteristics: presence of electrocardiogram (EKG) abnormalities, age, hypertension, prior cardiac history, smoking, diabetes mellitus, prior use of anthracyclines, and left-sided chest irradiation. RESULTS: Six of 61 women (10%) developed clinically reversible grade 3 CHF following infusional cyclophosphamide with a median percent decline in ejection fraction of 31%. Incidence of transient cyclophosphamide-related cardiac toxicity (10%) is comparable to previous recorded literature. Older age was significantly correlated with the CHF development; with median ages for the entire group and for patients developing CHF of 45 and 59, respectively. No association was found with other pretreatment characteristics. CONCLUSIONS: As a result of these findings, oncologists should carefully monitor fluid balance in older patients. Routine EKG monitoring during infusional cyclophosphamide did not predict CHF development.

Adult↗

PubMed2004

Survival and recurrence after breast cancer in BRCA1/2 mutation carriers.

BACKGROUND: Genetic mutation is responsible for approximately 10% of breast cancers. The purpose of this study was to compare breast cancer survival and recurrence rates between BRCA1/2 mutation carriers and noncarriers. METHODS: Using the Columbia Presbyterian breast cancer database, we collected the tissue blocks of all patients younger than 65 years of age and of Jewish descent. The patients were contacted and the data updated. DNA was extracted from the tissue blocks and tested for the common mutations. The results of the genetic mutation and updated database were anonymized and merged. The survival and recurrence rates were compared between mutation carriers and noncarriers. RESULTS: A total of 739 breast cancer cases in 715 patients were identified. We were able to test 487 patients. We identified 30 BRCA1 and 21 BRCA2 mutation carriers, for an incidence of 10.36%. The median follow-up for the patients tested was 50 months. BRCA1 patients more frequently had estrogen- and progesterone-negative tumors and had a higher incidence of positive nodes. BRCA1 patients received chemotherapy more frequently. The incidence of in situ disease was similar for mutation and non-mutation carriers. BRCA1/2 mutation carriers had a higher incidence of bilateral disease. There was no difference in 5- or 10-year overall and breast cancer-specific survival between mutation and non-mutation carriers. CONCLUSIONS: Breast cancer patients with BRCA1/2 mutations have a similar outcome as non-mutation carriers.

Adult↗

PubMed2003

Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene.

Malignant cells often display defects in autophagy, an evolutionarily conserved pathway for degrading long-lived proteins and cytoplasmic organelles. However, as yet, there is no genetic evidence for a role of autophagy genes in tumor suppression. The beclin 1 autophagy gene is monoallelically deleted in 40-75% of cases of human sporadic breast, ovarian, and prostate cancer. Therefore, we used a targeted mutant mouse model to test the hypothesis that monoallelic deletion of beclin 1 promotes tumorigenesis. Here we show that heterozygous disruption of beclin 1 increases the frequency of spontaneous malignancies and accelerates the development of hepatitis B virus-induced premalignant lesions. Molecular analyses of tumors in beclin 1 heterozygous mice show that the remaining wild-type allele is neither mutated nor silenced. Furthermore, beclin 1 heterozygous disruption results in increased cellular proliferation and reduced autophagy in vivo. These findings demonstrate that beclin 1 is a haplo-insufficient tumor-suppressor gene and provide genetic evidence that autophagy is a novel mechanism of cell-growth control and tumor suppression. Thus, mutation of beclin 1 or other autophagy genes may contribute to the pathogenesis of human cancers.

Alleles↗

PubMed2003

Ethnic neutropenia and treatment delay in African American women undergoing chemotherapy for early-stage breast cancer.

Disparities in breast cancer survival have been observed between African American and white women. There are also known differences in mean baseline white blood cell (WBC) count among racial and ethnic groups. If the WBC count falls below conventionally defined treatment thresholds for patients undergoing adjuvant chemotherapy, reduced doses or treatment delays may occur, which could lead to race-based differences in treatment duration. We used the tumor registry at Columbia-Presbyterian Medical Center to identify 1178 women with newly diagnosed stage I and II breast cancer from whom we collected base-line information for 73 African American women and 126 age- and tumor stage-matched white women. Of these women, 43 African American and 93 white women underwent adjuvant chemotherapy. African American women had statistically significantly lower WBC counts than white women at diagnosis (6.2 x 10(9)/L for African American women versus 7.4 x 10(9)/L for white women, difference = 1.2, 95% confidence interval [CI] = 0.2 to 1.2; P =.02) and after treatment (5.3 x 10(9)/L for African American women versus 6.4 x 10(9)/L for white women, difference = 1.1, 95% CI = 0.2 to 2.5; P =.03). Overall, African American women required a statistically significantly longer duration of treatment than white women (19 weeks versus 15 weeks, respectively, difference = 4 weeks, 95% CI = 0.5 to 7.2 weeks; P =.03). The lower baseline WBC counts and longer duration of treatment for early-stage breast cancer in African American women compared with those in white women result in lower dose intensity of treatment for African American women, possibly contributing to observed racial differences in breast cancer survival.

Adult↗

PubMed2003

A phase II trial of docetaxel and estramustine in patients with refractory metastatic breast carcinoma.

BACKGROUND: The similarity between the mechanism of action between docetaxel and estramustine generated the hypothesis of synergistic antimicrotubule effects and cytotoxicity when the two agents are combined. In addition, it has been demonstrated that estramustine binds P-glycoprotein in vitro and, thus, may prevent the efflux of taxanes in tumors that over-express P-glycoprotein. To further evaluate the combinations clinical efficacy and safety, a trial was performed in heavily pretreated patients with metastatic breast carcinoma (MBC). METHODS: Thirty-six patients with MBC were treated with estramustine 900 mg/m(2) per day divided into 3 doses given on Days 1-3 and docetaxel 70 mg/m(2) given by intravenous administration over 1 hour on Day 3 after the first dose of estramustine, every 21 days. Patients may have received any number of prior chemotherapy regimens for MBC. RESULTS: Nine partial responses were observed in 31 assessable patients, for an objective response rate of 29% (95% confidence interval, 14-48%). The median progression free survival was 4 months (range, 1-41 months), and the median overall survival was 17 months (range, 2-45 months). Severe toxicities (Grade 3 or 4) were neutropenia, hypophosphatemia, and thrombosis. Seventy-five percent of patients experienced either an improvement or no change in quality of life. CONCLUSIONS: The combination of docetaxel and estramustine produced responses in heavily pretreated women with MBC while maintaining quality of life.

Adult↗

PubMedDate not supplied

Relationship between mammographic breast density and tamoxifen in women with breast cancer.

Previous studies have reported that tamoxifen use is associated with a decrease in mammographic breast density. This is a potentially valuable finding since mammographic sensitivity is limited by breast density. Anything that reduces breast density would theoretically enhance the sensitivity of mammography for the detection of breast cancer in women at an earlier stage when it is more curable. We performed a retrospective study investigating the potential effect of tamoxifen on breast density. The data for this retrospective study were collected from the records of 52 charts from a single medical oncologist. Patients with breast cancer were selected regardless of stage or age at the time of diagnosis or treatment, as long as their charts had records of bilateral mammograms. For each breast on each woman, both mediolateral oblique and craniocaudal views were reviewed independently by two radiologists on two separate occasions to obtain inter- and intraobserver variability. Two methods of classifying breast density were used: the Breast Imaging Reporting and Data System (BI-RADS), and measurements of percent density. Only age and menopausal status were found to be associated with breast density. There was no correlation between breast density and tamoxifen use (past or present). Our study shows no association between tamoxifen use and breast density. We confirm previous observations that breast density is inversely correlated with age and postmenopausal status.

Adult↗

PubMedDate not supplied

Effectiveness of academic detailing on breast cancer screening among primary care physicians in an underserved community.

BACKGROUND: Urban minority groups, such as those living in northern Manhattan and the South Bronx, are generally underserved with regard to breast cancer prevention and screening practices. Primary care physicians are critical for the recommendation of mammography and clinical breast examinations to their patients. DESIGN: Two medically underserved communities were matched and block randomized. The aim of the study was to assess the efficacy of academic detailing in increasing recommendations for breast cancer screening in community-based primary care physicians. SETTING/PARTICIPANTS: Ninety-four primary care community-based (ie, not hospital-based) physicians in northern Manhattan were compared with 74 physicians in the South Bronx who received no intervention. INTERVENTION: INTERVENTION participants received multicomponent physician-directed education, academic detailing, using the American Cancer Society guidelines for the early detection of breast cancer. MAIN OUTCOME MEASURES: We administered interviews to ask about primary care physicians' recommendation of mammography and clinical breast examination. They were also queried about their knowledge of major risk factors and perceived barriers to breast cancer screening. We conducted medical audits of 710 medical charts 2 years before and after the intervention. RESULTS: Using a mixed models linear analysis, we found a statistically significant intervention effect on the recommendation of mammography and clinical breast examination (according to medical audit) by female patients age 40 and over. INTERVENTION group physicians correctly identified significantly more risk factors for breast cancer, and significantly fewer barriers to practice, than did comparison physicians. CONCLUSIONS: We found some evidence of improvement in breast cancer screening practices due to academic detailing among primary care physicians practicing in urban underserved communities.

Breast Neoplasms↗

PubMedDate not supplied

Cyclin D1 overexpression is associated with estrogen receptor expression in Caucasian but not African-American breast cancer.

BACKGROUND: African-American (AA) breast cancer patients consistently show a shortened survival when compared with Caucasian patients. This worse prognosis is most likely due to a combination of socioeconomic factors and differences in tumor biology. Previous studies have demonstrated that cyclin D1 overexpression is strongly associated with estrogen receptor (ER) expression in breast cancer, but these series either included primarily Caucasian patients or did not specify race. MATERIALS AND METHODS. We analyzed 200 breast cancer cases obtained from AA and Caucasian patients who were matched on age, stage, ER status, and year of diagnosis. We examined expression levels of cyclin D1, p53, p27Kip1 (p27), and p21Cip1 (p21), and correlated their expression with ER status. RESULTS: Cyclin D1, p53, p27, and p21 expression rates were similar in matched cases of AA and Caucasian breast cancer (p values>0.05). However, cyclin D1 overexpression was significantly associated with ER status in only the Caucasian (p=0.0005), and not the AA cases (p=0.07). CONCLUSION: This finding suggests a novel biological difference, which may contribute to the more aggressive phenotype of AA breast cancer.

Adult↗