Biomedical subjects

Georgiana K Ellis

Publications and source records attributed to Georgiana K Ellis.

11 recordsLinked to original sources

PubMed2006

Quantitative fluoroestradiol positron emission tomography imaging predicts response to endocrine treatment in breast cancer.

PURPOSE: In breast cancer, [(18)F]fluoroestradiol (FES) positron emission tomography (PET) correlates with estrogen receptors (ER) expression and predicts response to tamoxifen. We tested the ability of FES-PET imaging to predict response to salvage hormonal treatment in heavily pretreated metastatic breast cancer patients, predominantly treated with aromatase inhibitors. PATIENTS AND METHODS: Initial FES uptake measurements in 47 patients with ER-positive tumors were correlated with subsequent tumor response to 6 months of hormonal treatment. Most patients had bone dominant disease and prior tamoxifen exposure. Response was compared to initial FES-PET uptake, measured qualitatively and quantitatively using standardized uptake value (SUV) and estradiol-binding flux. RESULTS: Eleven of 47 patients (23%) had an objective response. While no patients with absent FES uptake had a response to treatment, the association between qualitative FES-PET results and response was not significant (P = .14). However, quantitative FES uptake and response were significantly associated; zero of 15 patients with initial SUV less than 1.5 responded to hormonal therapy, compared with 11 of 32 patients (34%) with SUV higher than 1.5 (P < .01). In the subset of patients whose tumors did not overexpress HER2/neu, 11 of 24 patients (46%) with SUV higher than 1.5 responded. CONCLUSION: Quantitative FES-PET can predict response to hormonal therapy and may help guide treatment selection. Treatment selection using quantitative FES-PET in our patient series would have increased the rate of response from 23% to 34% overall, and from 29% to 46% in the subset of patients lacking HER2/neu overexpression. A multi-institutional collaborative trial would permit definitive assessment of the value of FES-PET for therapeutic decision making.

Adult↗

PubMed2005

Residual tumor uptake of [99mTc]-sestamibi after neoadjuvant chemotherapy for locally advanced breast carcinoma predicts survival.

BACKGROUND: Studies utilizing serial [99mTc]-sestamibi (MIBI) scintimammography have reported accurate prediction of tumor response in patients with locally advanced breast carcinoma (LABC) undergoing neoadjuvant chemotherapy. The pathologic response of LABC to presurgical treatment regimens is a prognostic indicator of survival. The authors tested whether MIBI uptake posttherapy predicted survival. METHODS: Sixty-two patients with LABC underwent MIBI scintimammography just before chemotherapy and 2 months after treatment initiation. An additional MIBI scan was performed if treatment lasted >3 months. The affected breast was imaged within 10 minutes after injection to reflect early uptake, which the authors have shown to be related to tumor blood flow. MIBI uptake was quantified using the lesion-to-normal breast (L:N) ratio. Most patients (93%) received weekly dose-intensive doxorubicin-based treatment. Disease-free survival (DFS) and overall survival (OS) were compared with posttherapy primary MIBI uptake and with other established prognostic factors for neoadjuvantly treated LABC, namely, primary tumor pathologic response and posttherapy axillary lymph node status. RESULTS: Patients with high uptake on the last observed MIBI scan (i.e., the L:N ratio was greater than the median value) had poorer DFS and OS (P<0.01 and P=0.01, respectively). Residual MIBI uptake retained independent prognostic significance in preliminary multivariate analysis that included other established prognostic markers. CONCLUSIONS: High primary breast tumor MIBI uptake after neoadjuvant chemotherapy predicted poor survival, suggesting serial MIBI imaging may provide a useful quantitative surrogate end point for neoadjuvant chemotherapy trials. Given the association between MIBI uptake and tumor blood flow, this prognostic capability may be related to retained tumor vascularity after treatment.

Adult↗

PubMed2004

HER-2 testing in breast cancer using parallel tissue-based methods.

CONTEXT: Testing for HER-2 oncogene in breast cancer has increased because of its role as a prognostic and predictive factor. Some advocate gene testing by fluorescence in situ hybridization (FISH) vs protein testing by immunohistochemistry as the method which most accurately evaluates and predicts response to the anti-HER-2 antibody, trastuzumab. However, critical examination of FISH on a screening basis has yet to be performed. OBJECTIVES: To determine the correlation between FISH and immunohistochemistry results by determining HER-2/neu gene status on tumor sections with indeterminate immunohistochemistry results (2+ score), confirm gene amplification on tumor sections with positive results (3+ score), and verify gene status on tumor sections with negative results (0 or 1+ score). DESIGN, SETTING, AND PATIENTS: A quality control and quality assurance program for HER-2 testing by FISH, which used tumor specimens from 2963 patients (median age, 56 years) with breast cancer received from 135 hospitals and cancer centers in 29 states, was performed at a reference laboratory from January 1, 1999, to May 15, 2003. Every specimen evaluated by FISH was parallel tested with immunohistochemistry tests. MAIN OUTCOME MEASURES: With FISH as the presumed standard testing method, the positive and negative predictive values and sensitivity and specificity of immunohistochemistry were calculated. RESULTS: A total of 3260 clinical HER-2 tests by FISH were performed on 2963 serially referred breast cancer specimens. Of these, 2933 tests were successful and 2913 breast cancer specimens had both FISH and immunohistochemistry results available. With FISH as the standard testing method, the positive predictive value of positive immunohistochemistry score (3+) was 91.6%, and the negative predictive value of negative immunohistochemistry score (0 or 1+) was 97.2%. The sensitivity of immunohistochemistry tests, including tumor sections with scores of 2+ or 3+, was 92.6% and the specificity of immunohistochemistry tests with scores of 3+ was 98.8%. The FISH test had a significantly higher failure rate (5% vs 0.08%) and reagent cost (140 dollars vs 10 dollars), and longer testing (36 hours vs 4 hours) and interpretation times (7 minutes vs 45 seconds) vs immunohistochemistry tests. CONCLUSIONS: A testing algorithm for HER-2 determination is most efficient by using immunohistochemistry as the method of choice, with FISH performed for cancers with indeterminate results (2+ score). Successful quality control and quality assurance programs are a prerequisite for such approaches.

Adult↗

PubMed2004

Potential of chemotherapy-herb interactions in adult cancer patients.

GOALS OF WORK: The purpose of this study was to examine the specific herbs or vitamins (HV) used by patients receiving chemotherapy. Specifically, the following aspects were investigated: (1) HV use among adult cancer patients receiving chemotherapy, (2) the frequency of potential chemotherapy-HV interactions, (3) communication patterns between oncologists and their cancer patients taking HV, and (4) patients' reactions to two hypothetical scenarios of chemotherapy-HV interactions. PATIENTS AND METHODS: Adult cancer patients receiving chemotherapy at a university-based outpatient clinic over a 1-month period were sent a validated eight-page questionnaire regarding the use of complementary/alternative medicine, focusing on HV use. A total of 76 patients participated; relevant medical information was obtained from study participants' charts. The chemotherapy received was compared with HV use to assess for potentially detrimental chemotherapy-HV interactions. RESULTS: HV use in patients receiving chemotherapy was common (78%), with 27% of the study participants being at risk of a detrimental chemotherapy-HV interaction. Most patients (>85%) would discontinue their HV or ask their medical oncologist for advice if a detrimental chemotherapy-HV interaction was suspected. Although most patients discussed HV use with their oncologist, the majority also relied on their friends and naturopathic physician for information regarding HV. CONCLUSIONS: Considerable potential exists for detrimental chemotherapy-HV interactions. Methods to improve communication of HV use between cancer patients receiving chemotherapy and health-care practitioners are necessary to identify and minimize the risk of these interactions.

Adult↗

PubMed2004

Evaluation of the internal mammary lymph nodes by FDG-PET in locally advanced breast cancer (LABC).

The presence of internal mammary (IM) lymph node metastases in breast cancer predicts outcome and may alter treatment. Standard imaging has limited usefulness for evaluation of the IM chain because of low sensitivity. Our preliminary studies suggested that [F-18]-2-fluoro-d-glucose positron emission tomography (FDG-PET) improves the detection of IM and mediastinal metastases. We therefore performed a retrospective review of women who underwent FDG-PET prior to treatment to determine the benefit of PET for imaging IM disease. The records of 28 consecutive patients undergoing FDG-PET prior to neoadjuvant chemotherapy for suspected locally advanced breast cancer (LABC) were reviewed. The presence of abnormal IM uptake on FDG-PET was noted. IM uptake on FDG PET was compared with standard radiographic imaging and was correlated with putative risk factors for IM involvement and with clinical patterns of failure. Patients did not undergo IM biopsy; however, patterns of failure were assessed to validate the FDG-PET findings. Clearly abnormal FDG uptake in the IM nodes was seen in 7 of 28 women (25%). Prospective conventional chest imaging failed to identify IM metastases in any patient. IM uptake on PET was associated with large size of the primary tumor (P = 0.03) and with inflammatory disease (P = 0.04). The presence of IM FDG uptake predicted failure by a pattern consistent with spread from IM lymph node metastasis. FDG-PET appears to be a useful noninvasive modality to detect IM metastases in LABC. Pathologic verification in a prospective study is necessary to confirm these findings.

Adult↗

PubMed2003

Myalgias and arthralgias associated with paclitaxel.

Paclitaxel-induced myalgias and arthralgias occur in a significant fraction of patients receiving therapy with this taxane, potentially impairing physical function and quality of life. Paclitaxel-induced myalgias and arthralgias are related to individual doses; associations with the cumulative dose and infusion duration are less clear. Identification of risk factors for myalgias and arthralgias could distinguish a group of patients at greater risk, leading to minimization of myalgias and arthralgias through the use of preventive therapies. Optimal pharmacologic treatment and possibilities for the prevention of myalgias and arthralgias associated with paclitaxel are unclear, partially due to the small number of patients treated with any one medication. The effectiveness of nonsteroidal anti-inflammatory drugs (NSAIDs) is the most frequently documented pharmacologic intervention, although no clear choice exists for patients who fail to respond to NSAIDs. However, the increasing use of weekly paclitaxel could necessitate daily administration of NSAIDs for myalgias and arthralgias and leave patients at risk for adverse effects. This concern may also limit the use of corticosteroids for the prevention and treatment of paclitaxel-induced myalgias and arthralgias. Data from case reports suggest that gabapentin (Neurontin), glutamine, and, potentially, antihistamines (e.g., fexofenadine [Allegra]) could be used to treat and/or prevent myalgias and arthralgias. Given the safety profile of these medications, considerable enthusiasm exists for evaluating their effectiveness in the prevention and treatment of paclitaxel myalgias and arthralgias, particularly in the setting of weekly paclitaxel administration.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2003

Changes in blood flow and metabolism in locally advanced breast cancer treated with neoadjuvant chemotherapy.

UNLABELLED: Locally advanced breast cancer (LABC) is commonly treated with neoadjuvant chemotherapy followed by definitive surgery. The factors influencing the response of LABC to presurgical chemotherapy are incompletely understood. To characterize in vivo tumor biology in patients with LABC, we performed serial measurements of blood flow and glucose metabolism in LABC patients over the course of neoadjuvant chemotherapy and compared measurements with response. METHODS: Thirty-five patients with newly diagnosed LABC underwent (18)F-FDG and (15)O-water PET imaging before therapy and after 2 mo of chemotherapy. Tumor metabolism was estimated from graphical analysis of dynamic (18)F-FDG studies and was expressed as the metabolic rate of (18)F-FDG (MRFDG). Blood flow was estimated from dynamic images after bolus (15)O-water injection using a 1-compartment model. Metabolism and blood flow data were analyzed with and without partial-volume corrections to account for changes in tumor size over the course of therapy. Changes in tumor blood flow and metabolism were compared with response to chemotherapy and with patient survival. RESULTS: For all patients, the mean MRFDG after 2 mo of chemotherapy decreased by 54% and the mean blood flow by 21%. Responders showed a greater decline in MRFDG than did nonresponders; however, the difference was of borderline significance (P = 0.05) after correction for partial-volume effects. Patients who responded had a decline in tumor blood flow, whereas nonresponders had an average increase (-32% vs. +48%, P < 0.005); the difference between responders and nonresponders remained significant after partial-volume correction (P < 0.01). There was also a statistically significant association between the pathologic degree of response and the percentage change in blood flow at 2 mo with and without partial-volume correction; this was not the case for MRFDG. The change in blood flow after 2 mo of therapy predicted disease-free and overall survival. CONCLUSION: Although both resistant and responsive LABC tumors have an average decline in MRFDG over the course of chemotherapy, resistant tumors have an average increase in blood flow. Patients whose tumors fail to have a decline in blood flow after 2 mo of therapy have poorer disease-free and overall survival. Further investigations are needed to elucidate the tumor biology underlying these findings.

Adult↗

PubMed2002

Dose-dense anthracycline-based chemotherapy for node-positive breast cancer.

PURPOSE: Theoretical considerations and clinical experience suggest that dose-dense chemotherapy may be superior to other approaches using the same drugs. We studied a dose-dense combination of doxorubicin and cyclophosphamide, with or without fluorouracil, as adjuvant therapy. PATIENTS AND METHODS: Patients with resected breast cancer were treated if they were node-positive and estrogen receptor-negative, positive for overexpression of Her-2-neu, or had four or more involved nodes. Doxorubicin was given weekly to a total dose of 480 mg/m(2). Cyclophosphamide 60 mg/m(2) was given daily by mouth during the period of doxorubicin treatment. The first 30 patients received fluorouracil at 300 mg/m(2)/wk intravenously concurrently with doxorubicin administration. In the last 22, it was omitted because of symptomatic hand-foot syndrome in the majority of patients. Filgrastim (granulocyte colony-stimulating factor [G-CSF]) was administered during chemotherapy every day except the day of intravenous administration and continued until 1 week after the completion of the chemotherapy. RESULTS: Between October 20, 1992, and June 10, 1997, we enrolled 52 patients. The mean delivered dose-intensity for doxorubicin was 18.6 mg/m(2)/wk. Hospitalization was required in 6% of patients for reversible febrile neutropenia. There were no acute treatment-related deaths, but one patient subsequently died of acute leukemia with a characteristic translocation for anthracycline-related exposure. At 5 years, the event-free survival was 86% for all patients (95% confidence interval, 75% to 95%). CONCLUSION: Continuous dose-dense chemotherapy with G-CSF support produced encouraging results, which seem to be superior to those expected with "standard" doxorubicin and cyclophosphamide chemotherapy. It deserves a test in the form of a randomized trial where this approach to anthracycline-based treatment is compared with intermittent administration.

Adult↗

PubMed2002

[Tc-99m]-sestamibi uptake and washout in locally advanced breast cancer are correlated with tumor blood flow.

OBJECTIVES: To determine the influence of breast tumor blood flow on MIBI kinetics, we compared MIBI uptake and washout to [O-15]-water PET estimates of blood flow in patients with locally advanced breast cancer. METHODS: Prior to therapy, 37 patients underwent MIBI and [O-15]-water PET imaging; 22/37 also had MIBI washout analysis. Twenty-five patients underwent serial imaging over the course of chemotherapy. RESULTS: MIBI uptake and blood flow had a significant positive correlation pre-therapy. The change in MIBI uptake over the course of therapy also correlated with the change in blood flow. The half-time of MIBI washout inversely correlated with blood flow, indicating faster MIBI washout with higher blood flow. CONCLUSIONS: Blood flow strongly influences early MIBI uptake and can be a factor affecting the rate of MIBI washout in breast tumors. We present a model of MIBI kinetics in tumors which forms a hypothesis for further mechanistic studies of MIBI uptake and washout in breast cancer.

Blood Flow Velocity↗

PubMed2002

Blood flow and metabolism in locally advanced breast cancer: relationship to response to therapy.

UNLABELLED: Locally advanced breast cancer (LABC) is commonly treated with neoadjuvant chemotherapy followed by definitive surgery. The factors influencing the response of LABC to presurgical chemotherapy are incompletely understood. To characterize in vivo tumor biology in patients with LABC, we measured pretherapy blood flow and glucose metabolism in LABC, compared measurements with clinical and pathologic parameters, and examined blood flow and response to subsequent neoadjuvant chemotherapy. METHODS: Thirty-seven patients with newly diagnosed LABC underwent (18)F-FDG and (15)O-water PET imaging. Thirty-one of these patients underwent neoadjuvant chemotherapy, and response was evaluated by serial measurements of tumor size and pathologic examination after definitive surgery after chemotherapy. Tumor metabolism was estimated from graphic analysis of dynamic (18)F-FDG studies and was expressed as the metabolic rate of (18)F-FDG (MRFDG). Blood flow was estimated from dynamic images after bolus (15)O-water injection using a 1-compartment model. Tumor blood flow and metabolism were compared with clinical and pathologic parameters and with response to chemotherapy. RESULTS: Both blood flow and metabolism were significantly higher in tumor than in normal breast. Tumor blood flow and metabolism were correlated but highly variable. There were weak associations of metabolism with patient age and tumor grade and of blood flow with estrogen receptor status. There was a statistically significant trend for patients with a high MRFDG to have a poorer response to therapy (P = 0.001). Response was not significantly correlated with any other parameters. A low ratio of MRFDG to blood flow was the best predictor of macroscopic complete response (CR) (P = 0.02 vs. non-CR). Preliminary analysis of patient follow-up showed the ratio of MRFDG to blood flow to also be predictive of disease-free survival. CONCLUSION: Despite uniformly large tumor size, blood flow and metabolism in LABC are highly variable. High glucose metabolism predicts a poor response to neoadjuvant chemotherapy, and low MRFDG relative to blood flow is a predictor of CR. Further work is needed to elucidate the biologic mechanisms underlying these findings.

Adult↗

PubMedDate not supplied

Amphiphysin paraneoplastic syndrome: a delayed diagnosis of breast carcinoma.

We present a rare case of the paraneoplastic disorder, amphiphysin autoimmunity, which is associated with breast cancer. Amphiphysin is a presynaptic protein to which the body can form antibodies usually in cases of carcinoma, particularly of the breast and lung. The diagnosis of malignancy was delayed because of the complexity of the presenting neurologic symptoms related to the autoimmunity. The confusing picture and the rarity of the entity can result in delays in routine investigations, such as screening mammography. We advocate routine screening and physical examination in all patients, even in the presence of perplexing clinical symptoms.

Breast Neoplasms↗