Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this phase II study, the efficacy and tolerability of gemcitabine were studied in 42 patients with locally advanced or metastatic breast cancer who had received up to one prior chemotherapy regimen in an adjuvant setting. Ten patients had received adjuvant chemotherapy. Twenty-eight patients (67%) had visceral disease spread at entry. Gemcitabine (1000 mg/m2) was administered weekly on days 1, 8 and 15 of a 28-day cycle. The mean number of completed cycles was 3.9 and the mean dose delivered was 942.2 mg/m2. Ninety-seven percent of injections were administered as assigned. No complete responses were observed, but there were six partial responses and 24 patients with stable disease lasting 2-9 months. The overall response rate was 14.3% (95% CI 5.4-28.5%). The median survival for all patients was 15.2 months. Maximum WHO grade 3 and 4 toxicities were observed in five patients for nausea and vomiting, one patient for diarrhea, one patient for pain, seven patients for alanine transaminase, and eight patients for segmented neutrophils. There were no grade 3 and 4 toxicities for alopecia. These data confirm modest single-agent gemcitabine activity in advanced or metastatic breast cancer. Gemcitabine's favorable toxicity profile makes it an ideal candidate for combination chemotherapy.
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PMID:Phase II study of gemcitabine as first-line chemotherapy in patients with advanced or metastatic breast cancer. 1021 45

The underlying factor structure of a subset of 12 items, which comprise the psychosocial subscales of the EORTC QLQ-C30 was explored in a group of women, all with metastatic breast cancer who were participating in a psychosocial intervention study. Two main factors were identified in this exploratory factor analysis, representing "emotional distress" and "functional ability" dimensions. A preliminary assessment of the external validity of the two factor structure was undertaken. The results support the validity of a summative "emotional distress" and "functional ability" score in this sample of patients. The "functional ability" score discriminated well for subgroups defined by clinical status indicators (e.g., performance status, pain, chemotherapy treatment, fatigue). The "emotional distress" subscale discriminated with respect to suffering, fatigue and sleep disturbance. Both subscales converged with related concepts measured by independent instruments, providing support for convergent validity. Summative index scores may be advantageous for application in particular research situations; applying quality adjustments in health policy analyses; for screening purposes; to monitor populations and make comparisons across broad groups and as stratification variables in clinical trials. Further research to confirm the 2 factor structure is required in other samples before the interpretation can be accepted with confidence.
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PMID:Factor analysis of the psychosocial items of the EORTC QLQ-C30 in metastatic breast cancer patients participating in a psychosocial intervention study. 1047 63

Dose-time-volume relationships are probably the most heatedly debated single item in radiation oncology, with virtually no clinical or radiobiologic aspect of this subject that is not contentious in some way. There is even less agreement among oncologists about the treatment of patients with metastatic breast cancer. The goal of radiation therapy should be to relieve pain or restore function as quickly as possible, and treatments should be as short as possible to attain that goal. A summary of pertinent literature is given in this article. In addition to the decisions regarding dose, time, and field placement, the palliative treatment patients requires a value judgment, balancing quality of life against quantity of life. The effective clinician intuitively acts in favor of prolonging life, not prolonging death. Clinical judgement, comment sense, and a little humility for what we can accomplish with radiation therapy are probably more important than dose-time-volume relationships in the successful treatment of the dying patient with metastatic disease. Some of the important questions that must be asked to decide the appropriateness of a particular course of therapy are discussed.
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PMID:Radiation Therapy in the Management of Distant Breast Cancer Metastases. 1071 17

In metastatic breast cancer (MBC) doubling the epirubicin (EPI) dose intensity (DI) within the FEC (5-fluorouracil, EPI, cyclophosphamide) regimen could increase the response rate (RR) and ameliorate the quality of life (QoL) over standard FEC. From May, 1995, 74 consecutive patients with MBC were randomly treated with 6 courses of two FEC regimens containing 60 (60FEC) or 120 (120FEC, supported by primary G-CSF) mg/m2 of EPI. Drugs were administered every 21 days. The QoL was assessed over and after treatment by the EORTC QLQ-C30 (VER 2.0) and QLQ-BR23 questionnaires, compiled by the patient, and the Spitzer's QL-index, compiled by the physician. The study was prematurely closed in May, 1997, due to RR and QoL data of 4th interim analysis. The delivered EPI DI was 20.0 and 37.9 mg/m2/week in 60- and in 120FEC, respectively. Among the two regimens, there was no statistically significant difference in RR or in improvement of baseline overall QoL. With respect to 60FEC patients, the 120FEC patients had longer time to progression (19.2 vs 13.1 mos, p=0.04). Over baseline, the 120- but not the 60FEC patients had significantly greater pain decrease and lower deterioration of body image. In MBC, both 60- and 120FEC regimens furnished the same RR and improvement in overall baseline QoL. With respect to 60FEC patients, the 120FEC patients experienced longer time to progression. Over baseline, pain decrease and preservation of body image were also greater in these patients.
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PMID:Doubling of the epirubicin dosage within the 5-fluorouracil, epirubicin and cyclophosphamide regimen: a prospective, randomized, multicentric study on antitumor effect and quality of life in advanced breast cancer. 1071 47

Malignant osteolysis is a common complication of many cancers, most notably breast cancer, prostate cancer, and multiple myeloma. Hypercalcemia, pain, and fractures are the main manifestations. Malignant osteolysis can be fatal or cause a rapid deterioration in quality of life. The underlying mechanism in tumor cem-mediated activation of osteoclasts, whose function is normally to resorb bone. It follows that pharmacological agents capable of inhibiting osteoclast activity, including bisphosphonates, are likely to be useful in the treatment of malignant osteolysis. Also, experimental evidence suggest that bisphosphonates act on the tumor cells themselves, either by inhibiting mechanisms involved in the development of bone metastasis (tumor invasion, adhesion of tumor cells to the bone matrix) or by inducing apoptosis of tumor cells. Many clinical trials have found bisphophonates to be effective in the treatment of complications due to malignant osteolysis. Based on these studies, bisphosphonates are now indicated to treat hypercalcemia and to prevent skeletal complications of metastatic breast cancer and myeloma, in a dosage of 1600 mg.d orally for clodronate or 90 mg every four weeks intravenously for pamidronate. Osteoclast inhibition is clearly the mechanism underlying the efficacy of bisphosphonates in these clinical trials. Recent clinical trials found that prophylactic bisphosphonates therapy in patients with nonmetastasic breast cancer decreased the incidence of bone metastases, thus supporting a direct effect of biphosphonates on tumor cells. However, conflicting experimental and clinical data have been reported, so that it remains uncertain whether bisphosphonates have anti-tumor effects in vivo in humans. Nevertheless, biphosphonates now have an undisputed place in the therapeutic armamentarium for cancer.
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PMID:Mechanisms of action of bisphosphonates on tumor cells and prospects for use in the treatment of malignant osteolysis. 1077 65

The objective of the study was to determine possible differences in perception of quality of life (QoL) between patients with metastatic breast or prostate cancer, their partners, and the treating physician. Patients with metastatic breast cancer (n = 71), and metastatic prostate cancer (n = 29), a partner, and the physician each completed the same QoL questionnaire indicating how they perceived the patient's QoL. The European organization for research and treatment of cancer (EORTC) QLQ-C30 questionnaire was used to assess patients with breast cancer and the modified prostate cancer specific quality of life instrument (PROSQOLI) for patients with prostate cancer. There was reasonable agreement in mean scores between patients, and physicians or partners, for many domains of QoL; however, there was substantial discordance between scores when considering individual patients. For patients with metastatic breast cancer, physicians systematically underestimated overall QoL (p = 0.0002), social functioning (p = 0.001), and role functioning (p = 0.008), while partners showed better agreement. With prostate cancer physicians tended to underestimate pain, while mean scores for spouses were more concordant. There is substantial variability between ratings of QoL by physicians or partners, as compared to patient ratings. Medical decisions should be based on information about QoL provided by patients using validated methods.
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PMID:Perception of quality of life by patients, partners and treating physicians. 1133 25

An 83-year-old woman with a history of Alzheimer's disease and breast cancer died at home while receiving palliative pain therapy with oral morphine from her family for metastatic breast cancer. Allegations of mistreatment were made, and this case was ultimately referred to the Office of the Chief Medical Examiner, State of Maryland. An autopsy failed to identify any injuries or residual cancer, leaving no anatomic explanation for the pain that had been presumed to be metastatic breast carcinoma involving bone. The blood free morphine concentration was 5,200 ng/ml, and the total morphine concentration was 15,000 ng/ml. This case demonstrates the challenges and difficulties in forensic medicine when faced with the interpretation of toxicologic results at the end of life.
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PMID:Palliative pain therapy at the end of life and forensic medicine issues. 1144 65

Bone metastases represent a significant tumor-related complication affecting many breast cancer patients. The resulting bone destruction or osteolysis that frequently accompanies metastatic bone disease results in considerable morbidity for patients including a high rate of skeletal complications, severe pain, and a reduced quality of life. Traditionally, the treatment of metastatic bone disease has relied heavily on the use of multidisciplinary therapies, such as radiotherapy in combination with systemic treatment, supported by analgesia. Bisphosphonates are a class of pyrophosphate analogs that actively inhibit bone resorption. As a result, their clinical application has expanded greatly over the past 5 to 10 years and, in addition to being the treatment of choice for hypercalcemia of malignancy, they have been shown to be effective in reducing the skeletal morbidity associated with metastatic breast cancer. Furthermore, recent data from animal and in vitro studies suggest that bisphosphonates may actually have an antiapoptotic and antiproliferative effect not only on osteoclasts, but also on macrophages and tumor cells. Recent improvements in our understanding of the underlying molecular mechanisms in breast cancer, the diagnosis of the disease itself, and the development of new systemic therapies has led to improved survival benefit for many breast cancer patients. However, because survival duration has also been related to the risk of developing skeletal complications, bisphosphonates may play an ever greater role in the management and prevention of skeletal morbidity in the future.
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PMID:Factors influencing the role of bisphosphonates in breast cancer management. 1154 75

We compared the efficacy and safety of the oral aromatase inactivator exemestane (EXE) with megestrol acetate (MA) in women with metastatic breast cancer. This phase III randomized, double-blind, multicenter study was conducted in 769 postmenopausal women who had experienced tamoxifen failure. Treatment arms consisted of EXE 25 mg once daily (n=366) or MA 40 mg four times daily (160 mg daily; n=403). Peer-reviewed, intent-to-treat analyses demonstrated that EXE induced a trend toward higher rates of complete response (CR)+partial response (PR) (15.0% vs. 12.4%) and of CR+PR+stable disease (SD)=24 weeks (37.4% vs. 34.6%), but differences were not statistically significant. Statistically significant differences favoring EXE were seen in median duration of CR+PR+SD=24 weeks (60.1 vs. 49.1 weeks; P=0.025), time to tumor progression (20.3 vs. 16.6 weeks; P=0.037), time to treatment failure (16.3 vs. 15.7 weeks; P=0.042), and overall survival (not reached vs. 123.4 weeks; P=0.039). Both treatments were well tolerated, but MA was associated with more grade 3 or 4 weight gain (8% vs. 17%, P=0.001); the pain score was sim-ilar in both groups. There was a trend toward superiority in treatment-related signs and symptoms (TRSS) with EXE. There was greater improvement in the pain score and TRSS in patients achieving an objective response with EXE vs. MA. Quality of life improved or was similar for EXE in most domains. Exemestane offers an important new treatment option for postmenopausal women with hormone-responsive breast cancer.
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PMID:Exemestane improves survival in metastatic breast cancer: results of a phase III randomized study. 1197 Jul 44

Bisphosphonates (BPs) are potent inhibitors of osteoclast-mediated bone resorption, and it is well accepted that tumor cells in bone, especially breast cancer and myeloma cells, can stimulate osteoclast formation and activity leading to the release of growth factors or cytokines, which will further stimulate cancer cells' growth and their secretion of osteolytic factors. BPs are now the standard treatment for cancer hypercalcemia, for which a dose of 90 mg of pamidronate or 1500 mg of clodronate is recommended; the former compound is more potent and has a longer lasting effect. Repeated pamidronate infusions exert clinically relevant analgesic effects in more than half of patients with metastatic bone pain. Recent data suggest that non-responding patients should perhaps be treated with higher doses. The optimal dose actually remains to be defined, especially as it is thought that it is probably a function of the disease stage. Regular pamidronate infusions can also achieve a partial objective response according to conventional UICC criteria and they can almost double the objective response rate to chemotherapy. Lifelong administration of oral clodronate to patients with breast cancer metastatic to bone reduces the frequency of morbid skeletal events by more than one-fourth. Two double-blind randomized placebo-controlled trials comparing monthly 90 mg pamidronate infusions to placebo infusions for 1-2 years in addition to hormone or chemotherapy in patients with at least one lytic bone metastasis have shown that the mean skeletal morbidity rate could be reduced by 30-40%. The results obtained with intravenous BPs are generally viewed as better than those obtained with oral clodronate. However, preference can be given to the oral route when BPs are started early in the process of metastatic bone disease in a patient receiving hormone therapy. According to the recently published ASCO guidelines, pamidronate 90 mg i.v. delivered over 2 h every 3-4 weeks can be recommended in patients with metastatic breast cancer who have imaging evidence of lytic destruction of bone and who are concurrently receiving systemic therapy with hormonal therapy or chemotherapy. Furthermore, the ASCO Panel considered it "reasonable" to start i.v. BPs in women with localized pain whose bone scans were abnormal and plain radiographs normal, but not when an abnormal bone scan is asymptomatic. The pertinence of these criteria is discussed below. Because BPs are providing supportive care, reducing the rate of skeletal morbidity but evidently not abolishing it, the criteria for stopping their administration have to be different from those used for classic antineoplastic drugs, and they should not be stopped when metastatic bone disease is progressing. However, criteria to determine whether and for how long an individual patient benefits from their administration are lacking. New biochemical markers of bone resorption might help identify those patients continuing to benefit from therapy. Even better results have been achieved in patients with multiple myeloma, and the general consensus is that BPs should be started as soon as the diagnosis of lytic disease is made in myeloma patients. On the other hand, data are scanty in prostate cancer, but large-scale trials with potent BPs are ongoing or planned in such patients. Similar results to those achieved with pamidronate have been obtained with monthly 6-mg infusions of the newer BP ibandronate in patients with breast cancer metastatic to bone. The tolerance of ibandronate could be better, and the drug has the potential to be administered as a 15- to 30-min infusion. Zoledronate can also be administered safely as a 15-min 4-mg infusion, and large scale phase III trials have just been completed. These newer BPs will simplify the current therapeutic schemes and improve the cost-effectiveness ratio; they also have the potential to improve the therapeutic efficacy, at least in patients with an aggressive osteolytic disease or when given as adjuvant therapy. For that matter, initial data with clodronate indicate that they have the potential to prevent the development of bone metastases, but the use of BPs in the adjuvant setting must still be viewed as experimental.
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PMID:Bisphosphonates for cancer patients: why, how, and when? 1213 23


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