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Biomedical subjects

Harold J Burstein

Publications and source records attributed to Harold J Burstein.

34 records · Page 2Linked to original sources
PubMed2003

Trastuzumab and vinorelbine as first-line therapy for HER2-overexpressing metastatic breast cancer: multicenter phase II trial with clinical outcomes, analysis of serum tumor markers as predictive factors, and cardiac surveillance algorithm.

PURPOSE: Trastuzumab-based therapy improves survival for women with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer. We conducted a multicenter phase II study to evaluate the efficacy and safety of trastuzumab combined with vinorelbine, and to assess cardiac surveillance algorithms and tumor markers as prognostic tools. PATIENTS AND METHODS: Patients with HER2-positive (immunohistochemistry [IHC] 3+-positive or fluorescence in situ hybridization [FISH]-positive) metastatic breast cancer received first-line chemotherapy with trastuzumab and vinorelbine to determine response rate. Eligibility criteria were measurable disease and baseline ejection fraction >or= 50%. Serial testing for HER2 extracellular domain (ECD) was performed. RESULTS: Fifty-four women from 17 participating centers were entered onto the study. The overall response rate was 68% (95% confidence interval, 54% to 80%). Response rates were not affected by method of HER2 status determination (FISH v IHC) or by prior adjuvant chemotherapy. Median time to treatment failure was 5.6 months; 38% of patients were progression free after 1 year. Concurrent therapy was quite feasible with maintained dose-intensity. Patients received both chemotherapy and trastuzumab on 90% of scheduled treatment dates. Two patients experienced cardiotoxicity in excess of grade 1; one patient experienced symptomatic heart failure. A surveillance algorithm of screening left ventricular ejection fraction (LVEF) at 16 weeks successfully identified women at risk for experiencing cardiotoxicity. Other acute and chronic side effects were tolerable. Lack of decline in HER2 ECD during cycle 1 predicted tumor progression. CONCLUSION: Trastuzumab and vinorelbine constitute effective and well-tolerated first-line treatment for HER2-positive metastatic breast cancer. Patients with normal LVEF can be observed with surveillance of LVEF at 16 weeks to identify those at risk for cardiotoxicity.

Adult↗
PubMed2003

Central nervous system metastases in women who receive trastuzumab-based therapy for metastatic breast carcinoma.

BACKGROUND: Women with HER-2 overexpressing metastatic breast carcinoma benefit from trastuzumab-based therapy, but trastuzumab does not cross the blood-brain barrier. The authors characterized central nervous system (CNS) disease in these women. METHODS: Using pharmacy records, the authors retrospectively identified 153 women treated with trastuzumab alone or with chemotherapy for HER-2-positive metastatic breast carcinoma at Dana-Farber Partners Cancer Care from June 1998 to December 2000. A study cohort of 122 patients was identified after excluding patients without adequate clinical follow-up or who had CNS disease before trastuzumab treatment. Central nervous system disease was defined as one or more brain metastases or as leptomeningeal carcinomatosis. The median follow-up of this cohort was 23 months. RESULTS: Central nervous system metastases were identified in 34% of patients (95% confidence interval, 26-44%) at a median of 16 months after diagnosis of metastatic breast carcinoma and 6 months from the beginning of trastuzumab therapy. Ninety-three percent of patients with CNS disease presented with clinical symptoms. Five percent of patients with CNS disease had leptomeningeal involvement alone, although 14% had leptomeningeal involvement and parenchymal brain metastases. Fifty percent of patients were responding or had stable disease while receiving trastuzumab at other disease sites at the time of diagnosis of CNS metastasis. The median survival period after CNS metastases was 13 months. Fifty percent of patients died of progressive CNS disease. Patients receiving trastuzumab as first-line therapy for metastatic disease frequently developed brain metastases while responding to or stable on trastuzumab at other disease sites. CONCLUSIONS: Metastatic breast carcinoma to the CNS is common among patients receiving trastuzumab-based therapy, including patients responding to therapy outside the CNS. This may be due either to predilection for the CNS by HER-2-positive tumor cells and/or poor penetration of the CNS by trastuzumab or to improved visceral disease control leading to a longer life and onset of late tumor spread to the CNS. Efforts to characterize other risk factors for development of CNS disease, optimal screening algorithms, and new treatment strategies may be warranted.

Antibodies, Monoclonal↗
PubMed2003

Quality of non-breast cancer health maintenance among elderly breast cancer survivors.

PURPOSE: To assess the quality of preventive health care, the role of health care participation, and the patient and provider characteristics associated with high-quality care for breast cancer survivors. METHODS: We analyzed the 1997 to 1998 Medicare data of elderly women who were diagnosed with nonmetastatic breast cancer in 1991 or 1992 while living in a Survival, Epidemiology, and End Results (SEER) tumor registry area and who survived to the end of 1998 without evidence of cancer recurrence. Controls were matched for age, race, and geographic location. RESULTS: The 5,965 breast cancer survivors received more preventive services (influenza vaccination, lipid testing, cervical and colon screening, and bone densitometry) than matched controls. Among both groups, those who were younger, non-African-American, of higher socioeconomic status, living in urban areas, and receiving care in a teaching center were most likely to receive high-quality health maintenance. Those survivors who continued to see oncology specialists were more likely to receive appropriate follow-up mammography for their cancer, but those who were monitored by primary care physicians were more likely to receive all other non-cancer-related preventive services. Those who saw both types of practitioners received more of both types of services. When the control group was restricted only to women actively undergoing mammographic screening before the study period, receipt of preventive services was similar. CONCLUSION: Breast cancer survivors receive high-quality preventive services, but disparities on the basis of nonmedical factors still exist. Cancer follow-up may provide regular contact with the health system, maximizing the likelihood of receiving appropriate general medical care.

Aged↗
PubMed2003

Preoperative therapy with trastuzumab and paclitaxel followed by sequential adjuvant doxorubicin/cyclophosphamide for HER2 overexpressing stage II or III breast cancer: a pilot study.

PURPOSE: Trastuzumab combined with chemotherapy improves outcomes for women with human epidermal growth factor receptor 2 (HER2) overexpressing advanced breast cancer. We conducted a pilot study of preoperative trastuzumab and paclitaxel, followed by surgery and adjuvant doxorubicin and cyclophosphamide chemotherapy in earlier stage breast cancer. PATIENTS AND METHODS: Patients with HER2-positive (2+ or 3+ by immunohistochemistry) stage II or III breast cancer received preoperative trastuzumab (4 mg/kg x 1, then 2 mg/kg/wk x 11) in combination with paclitaxel (175 mg/m(2) every 3 weeks x 4). Patients received adjuvant doxorubicin and cyclophosphamide chemotherapy following definitive breast surgery. Clinical and pathologic response rates were determined after preoperative therapy. Left ventricular ejection fraction and circulating levels of HER2 extracellular domain were measured serially. RESULTS: Preoperative trastuzumab and paclitaxel achieved clinical response in 75% and complete pathologic response in 18% of the 40 women on study. HER2 3+ tumors were more likely to respond than 2+ tumors (84% v 38%). No unexpected treatment-related noncardiac toxicity was encountered. Four patients developed grade 2 cardiotoxicity (asymptomatic declines in left ventricular ejection fraction). Baseline HER2 extracellular domain was elevated in 24% of patients and declined with preoperative therapy. Immunohistochemical analyses of posttherapy tumor specimens indicated varying patterns of HER2 expression following trastuzumab-based treatment. CONCLUSION: Preoperative trastuzumab and paclitaxel is active against HER2 overexpressing early-stage breast cancer and may be feasible as part of a sequential treatment program including anthracyclines. The observed changes in cardiac function merit further investigation. Correlative analyses of HER2 status may facilitate understanding of tumor response and resistance to targeted therapy.

Adult↗
PubMed2003

Use of the peroxisome proliferator-activated receptor (PPAR) gamma ligand troglitazone as treatment for refractory breast cancer: a phase II study.

PURPOSE: To evaluate the therapeutic effects of the peroxisome proliferator-activated receptor (PPAR) gamma activating ligand, troglitazone, in patients with refractory metastatic breast cancer. EXPERIMENTAL DESIGN: Patients with advanced breast cancer refractory to at least one chemotherapy regimen (ER negative tumors) or two hormonal regimens (ER positive tumors) were treated with troglitazone at 800 mg p.o. QD until disease progression, to determine the percentage of patients free of progression at 6 months. Tumor response, toxicity, and changes in serum tumor markers (CEA, CA27.29) that might reflect alteration in tumor differentiation, were also examined. RESULTS: Twenty-two patients were enrolled before suspension of protocol accrual and treatment when troglitazone was withdrawn from commercial availability following FDA warnings on hepatic toxicity. No objective responses (CR or PR) were observed; only three patients had SD at 8 weeks. Patients came off study for PD (16), DLT (1), FDA withdrawal (2), or other (3) reasons. No patients took troglitazone for more than 20 weeks; all had experienced disease progression or began other systemic therapy within 6 months. All patients with elevated serum tumor markers (CEA and CA27.29) at baseline had rising tumor markers within 8 weeks. CONCLUSIONS: While clinical trials among different patient populations might uncover subtle effects on tumor differentiation, PPARgamma activation by troglitazone has little apparent clinical value among patients with treatment-refractory metastatic breast cancer.

Administration, Oral↗
PubMed2003

Follow-up care of breast cancer survivors.

Breast cancer survivors may have several medical and psychosocial concerns in follow-up care. Women with a history of breast cancer should be followed for local-regional recurrence or metastatic disease, as well as for the development of a second primary breast cancer in the contralateral breast. Regular follow-up visits can foster an ongoing patient-clinician relationship both to ensure adequate surveillance and so that symptoms of recurrence or complications of therapy will be reported by the patient and addressed promptly. There are multiple possible long-term complications that may arise following breast cancer treatment, many of which may be ameliorated with various therapies. Clinicians can also provide guidance and counseling as well as psychosocial support to patients regarding medical and psychosocial decisions that may be affected by their personal history of breast cancer.

Breast Neoplasms↗
PubMed2003

Trastuzumab regimens for HER2-overexpressing metastatic breast cancer.

Combination treatment with chemotherapy and trastuzumab is now standard therapy for the first-line treatment of women with HER2-overexpressing metastatic breast cancer. Combination therapy with trastuzumab has been shown to increase response rates, time to progression, quality of life, and overall survival for such patients. Several combination regimens have been developed, and newer combination regimens have recently been reported and are being studied in ongoing clinical trials. Newer trastuzumab-based regimens include triplet combinations with taxanes and platinum salts and regimens combining other innovative therapies. Among the increasing array of available combinations, several have proven appropriate for first-line therapy. To date, the optimal combination region has not been defined. Moreover, several questions remain regarding best scheduling, treatment duration, and use of trastuzumab at disease progression. This review briefly outlines the evolving role of trastuzumab in the treatment of HER2-overexpressing metastatic breast cancer.

Antibodies, Monoclonal↗
PubMed2002

American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for women with hormone receptor-positive breast cancer: status report 2002.

OBJECTIVE: To conduct an evidence-based technology assessment to determine whether the routine use of anastrozole or any of the aromatase inhibitors in the adjuvant breast cancer setting is appropriate for broad-based conventional use in clinical practice. POTENTIAL INTERVENTIONS: Anastrozole, letrozole, and exemestane. OUTCOMES: Outcomes of interest include breast cancer incidence, breast cancer-specific survival, overall survival, and net health benefit. EVIDENCE: A comprehensive, formal literature review was conducted for relevant topics and is detailed in the text. Testimony was collected from invited experts and interested parties. The American Society of Clinical Oncology (ASCO)-prescribed technology assessment procedure was followed. BENEFITS/HARMS: The ASCO panel recognizes that a woman and her physician's decision regarding adjuvant hormonal therapy is complex and will depend on the importance and weight attributed to information regarding both cancer and non-cancer-related risks and benefits. CONCLUSION: The panel was influenced by the compelling, extensive, and long-term data available on tamoxifen. Overall, the panel considers the results of the Arimidex (anastrozole) or Tamoxifen Alone or in Combination (ATAC) trial and the extensive supporting data to be very promising but insufficient to change the standard practice at this time (May 2002). A 5-year course of adjuvant tamoxifen remains the standard therapy for women with hormone receptor-positive breast cancer. The panel recommends that physicians discuss the available information with patients, and, in making a decision, acknowledge that treatment approaches can change over time. Individual health care providers and their patients will need to come to their own conclusions, with careful consideration of all of the available data. (Specific questions addressed by the panel are summarized in Appendix 3.) VALIDATION: The conclusions of the panel were endorsed by the ASCO Health Services Research Committee and the ASCO Board of Directors.

Anastrozole↗
PubMed2002

American Society of Clinical Oncology technology assessment of pharmacologic interventions for breast cancer risk reduction including tamoxifen, raloxifene, and aromatase inhibition.

OBJECTIVE: To update an evidence-based technology assessment of chemoprevention strategies for breast cancer risk reduction. POTENTIAL INTERVENTIONS: Tamoxifen, raloxifene, aromatase inhibition, and fenretinide. OUTCOMES: Outcomes of interest include breast cancer incidence, breast cancer-specific survival, overall survival, and net health benefit. EVIDENCE: A comprehensive, formal literature review was conducted for relevant topics. Testimony was collected from invited experts and interested parties. The American Society of Clinical Oncology (ASCO) prescribed technology assessment procedure was followed. VALUES: More weight was given to published randomized trials. BENEFITS/HARMS: A woman's decision regarding breast cancer risk reduction strategies is complex and will depend on the importance and weight attributed to information regarding both cancer- and noncancer-related risks and benefits. CONCLUSIONS: For women with a defined 5-year projected breast cancer risk of > or= 1.66%, tamoxifen (at 20 mg/d for 5 years) may be offered to reduce their risk. Risk/benefit models suggest that greatest clinical benefit with least side effects is derived from use of tamoxifen in younger (premenopausal) women (who are less likely to have thromboembolic sequelae and uterine cancer), women without a uterus, and women at higher breast cancer risk. Data do not as yet suggest that tamoxifen provides an overall health benefit or increases survival. In all circumstances, tamoxifen use should be discussed as part of an informed decision-making process with careful consideration of individually calculated risks and benefits. Use of tamoxifen combined with hormone replacement therapy or use of raloxifene, any aromatase inhibitor or inactivator, or fenretinide to lower the risk of developing breast cancer is not recommended outside of a clinical trial setting. This technology assessment represents an ongoing process and recommendations will be updated in a timely matter. VALIDATION: The conclusions were endorsed by the ASCO Health Services Research Committee and the ASCO Board of Directors.

Antineoplastic Agents, Hormonal↗
PubMed2002

Gemcitabine-induced radiation recall.

PURPOSE: To study and report 6 patients with radiation recall in unique sites, secondary to gemcitabine chemotherapy. METHODS AND MATERIALS: The clinical presentations and outcomes of 6 patients with radiation recall secondary to gemcitabine chemotherapy were retrospectively analyzed over the course of a 1-year period. RESULTS: Radiation recall reactions were seen in the central nervous system, skin, gastrointestinal tract, and in the lymphatic and musculoskeletal systems. The time between initiation of radiation and recall of the radiation phenomenon ranged from 3 weeks to 8 months from the time gemcitabine was initiated. The usual dosage of gemcitabine in these cases was 1000 mg/m(2) given on a weekly basis. No radiation therapy was given concomitantly with gemcitabine. Treatment of the recall reaction consisted of discontinuing gemcitabine and initiating steroid therapy, supportive therapy, and/or nonsteroidal anti-inflammatory agents. Minimal improvement was seen in 3 out of 6 patients, and resolution of the radiation recall was seen in 3 out of 6 patients. A comprehensive review of the literature revealed that radiation recall with gemcitabine has been related to skin reactions only; no previous cases of radiation recall occurring in the central nervous system have been reported with any chemotherapy agent. CONCLUSION: Radiation recall from gemcitabine chemotherapy is rare, but can potentially arise in any site that has been previously irradiated. Treating physicians must be aware of this potential toxicity from gemcitabine and radiation and discontinue the gemcitabine if radiation recall is observed.

Adult↗
PubMed2002

HER2 overexpressing metastatic breast cancer.

More than 40,000 women in the United States die each year from metastatic breast cancer. Elucidation of HER2 and its role in malignant transformation has helped define a subset of aggressive breast cancer that may be relatively resistant to non-anthracycline-based therapies and hormonal agents, but responds to targeted molecular therapy. Trastuzumab, an antibody against HER2, has proven effective as single agent therapy in women with HER2 overexpressed metastatic breast cancer. Moreover, in combination with chemotherapy, trastuzumab has been shown to delay disease progression and improve overall survival for women with HER2-positive advanced breast cancer. The combination of chemotherapy and trastuzumab is emerging as a standard of care in women with HER2 overexpressed metastatic breast cancer. Several combination regimens using trastuzumab with taxanes, vinca alkaloids, or platinum compounds have demonstrated efficacy in first- and second-line treatment settings. However, the development of anthracycline-based combinations has been limited by concerns of related cardiotoxicity. Newer multi-agent regimens are in development. The optimal combination, duration, and sequence of trastuzumab therapy remain unknown in patients with HER2-positive metastatic disease. The role of continuing treatment after disease progression is also unclear. Evidence from some retrospective analyses suggest HER2-positive tumors are relatively resistant to tamoxifen and perhaps more responsive to aromatase inhibitors, although such data are inconclusive. HER2 status should not be used routinely for clinical decision making regarding hormonal therapy options. Several ongoing trials are attempting to address these and other issues related to HER2 testing to select the most appropriate candidates for these emerging therapies. While many questions remain, the treatment of HER2 overexpressing metastatic breast cancer is rapidly evolving, and represents a new approach to treatment in oncology.

Antibodies, Monoclonal↗
PubMed2002

Treatment of breast cancer during pregnancy.

The management of breast cancer during pregnancy is one of the great clinical challenges in oncology. Patients are best served by care provided through a multidisciplinary team including surgeons, oncologists, obstetricians and genetics counsellors with experience in caring for similar women. The risks of diagnostic and therapeutic interventions can be mitigated by the consideration of known side effects of therapy on the fetus and the mother. However, because of the limited amount of clinical experience available, the potential risks to the patient, to the fetus and to the pregnancy are difficult to quantify. Treatment decisions need to be tailored carefully to the individual, respecting both her clinical circumstances and her personal preferences.

Animals↗