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)

A phase II study was conducted to assess the toxicity and response rate of vinorelbine (NavelbineR) combined with epirubicin and fluorouracil (NEF) in metastatic breast cancer. Vinorelbine was delivered at a dose of 25 mg/m2 on days 1 and 8, epirubicin at 60 mg/m2 on day 1 and fluorouracil at 600 mg/m2 on day 1, at 3-week intervals. Forty consecutive ambulant patients with breast cancer with measurable metastases were treated with a total of 310 cycles (median 8) as first-line therapy. The objective response rate was 83% (95% CI 71-95) (6/40 CR 15%, 27140 PR 68%). In 3 patients, CNS metastases were detected during NEF therapy those who had a partial response in their visceral metastases. Median time to progression was 13 months (95% CI 7-19) and estimated median survival time was 32 months. The main dose-limiting adverse effect, grade III-IV haematological toxicity, was reported in 92% of patients. One patient died of neutropenic sepsis. Grade III infections requiring hospitalization were observed in 8 patients (20%). Half of the patients complained of mild constipation, nausea or stomatitis, which were easily managed. Almost all patients had grade III alopecia. One patient with previous adjuvant anthracycline therapy (CEF x 9 two years earlier) developed fatal grade IV cardiac failure associated with pulmonary emboli 2 months after completion of NEF therapy (PR with 6 cycles). In line with the observations of others conducting phase II first-line trials combining vinorelbine and epirubicin, it is concluded that the NEF regimen is effective in metastatic breast cancer. Haematological toxicity, however, requires dose reductions in many patients. Furthermore, careful monitoring of cardiac function is necessary, particularly in patients who received prior adjuvant anthracycline therapy.
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PMID:Vinorelbine, epirubicin and fluorouracil as first-line therapy in metastatic breast cancer--a phase II trial. 1289 2

As in female patients, the clinical course in male patients with breast cancer is determined mainly by tumor stage. The literature contains very limited data on either the occurrence or the treatment of CNS metastases. This paper presents the case report of a 69-year-old man with multiple brain metastases 7 years after a diagnosis of lymph-node positive breast cancer, which had earlier already spread to the bones and liver. Whole-brain irradiation with a total dose of 30Gy resulted in palliation of symptoms. Nevertheless, survival was very short (7 weeks from diagnosis). Patients with metastatic breast cancer are at risk for the development of brain metastases. When performance status is poor the survival of patients with brain metastases is very limited. Treatment recommendations are the same as those for female patients with brain metastases from breast cancer.
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PMID:Report of a male patient with brain metastases from breast cancer. 1465 51

Central nervous system (CNS) metastases from breast cancer are common and can present as the first or solitary site of disease progression. The CNS has been reported to act as a sanctuary site that denies access to many chemotherapeutic agents. We present here, a series of 10 metastatic breast cancer patients who developed CNS metastases after an initial response to trastuzumab treatment. Forty one patients with metastatic HER2-overexpressing breast cancer, without evidence of CNS involvement prior to the initiation of trastuzumab treatment, were followed during trastuzumab treatment. A neurological evaluation was performed in those patients who developed neurological signs or symptoms during the course of treatment. The clinical course and pattern of CNS involvement in these patients are discussed. Thirty two patients (78%) showed an initial response to trastuzumab treatment. Ten (31%) of the responding patients developed either isolated CNS relapse or concurrent CNS and systemic progression at a median of 43 weeks after the initiation of trastuzumab treatment. Trastuzumab as a single agent was continued following control of brain symptoms in three patients, two showed signs of systemic disease progression at 11 and 15 weeks following the diagnosis of CNS metastases, respectively. In two other patients, trastuzumab in combination with weekly chemotherapy was continued for more than 20 weeks after CNS relapse without evidence of disease progression. The incidence of CNS involvement in our group of patients was higher than expected. With more successful and prolonged systemic anti-tumour effects achieved by novel drug combinations, the risk of developing CNS metastases might be even greater. Evaluation of prophylactic cranial irradiation strategies might be studied for high-risk patients.
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PMID:Central nervous system progression among patients with metastatic breast cancer responding to trastuzumab treatment. 1474 56

As systemic therapy of metastatic breast cancer improves, CNS involvement is becoming a more widespread problem. This article summarizes the current knowledge regarding the incidence, clinical presentation, diagnosis, prognosis, and treatment of CNS metastases in patients with breast cancer. When available, studies specific to breast cancer are presented; in studies in which many solid tumors were evaluated together, the proportion of patients with breast cancer is noted. On the basis of data from randomized trials and retrospective series, neurosurgery and stereotactic radiosurgery (SRS) may prolong survival in patients with single brain metastases. The treatment of multiple metastases remains controversial, as does the routine use of whole-brain radiotherapy (WBRT) after either surgery or SRS. Although it is widely assumed that chemotherapy is of limited benefit, data from case series and case reports suggest otherwise. WBRT, neurosurgery, SRS, and medical therapy each have a role in the treatment of CNS metastases; however, neurologic symptoms frequently are not fully reversible, even with appropriate therapy. Studies specifically targeted toward this group of patients are needed.
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PMID:CNS metastases in breast cancer. 1533 11

Fifteen per cent of metastatic breast cancer will develop symptomatic leptomeningeal metastases. The introduction of trastuzumab (Herceptin) therapy has improved the response rates of survival of patients with metastatic breast cancer overexpressing HER2. Although previous studies are retrospective and of limited number, involving small study groups and different types of patient management, several authors have reported a 30% incidence of leptomeningeal metastases in patients with metastatic breast cancer overexpressing HER2 who were treated with trastuzumab, while 70 to 80% of cases of the disease were controlled systemically. In order to improve control of the disease at the level of the central nervous system (CNS), routine detection of leptomeningeal metastases in high-risk patients could be offered. CA 15-3 in cerebrospinal fluid (CSF) detection might be useful in helping to diagnose CNS metastases, particularly where cytology results are negative--which applies to 30% of cases--because tumor markers are more sensitive in detecting the tumor process. Our study validate CA 15-3 measurement in CSF and reference values were given.
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PMID:[Early detection of leptomeningeal metastasis in patients with metastatic breast carcinoma: validation of CA 15-3 measurement in cerebrospinal fluid]. 1803 11

Brain metastasis occurs in 15-40% of cancer patients and is present in approximately 10-16% of patients with metastatic breast disease. However, little is known about prognostic factors enabling the early identification of breast cancer patients at risk of CNS metastases. Therapy for brain metastases should be based on several parameters, such as the assessment of prognostic variables, the extent of neurological and systemic disease, and its chemo-sensitivity to previously administered chemotherapy treatments. In view of the known close correlation between metastatic and primary tumor chemosensitivity, the type of chemotherapy chosen should depend more on the tumor histology than on the cerebral distribution of the single drug. More recent drugs with a high impact on the clinical outcome of metastatic breast cancer patients, such as taxanes or trastuzumab, play only a limited role in the treatment of brain metastases.
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PMID:Chemotherapy in breast cancer patients with brain metastases: have new chemotherapic agents changed the clinical outcome? 1855 Mar 83

Central nervous system (CNS) metastases are a major concern in patients with stage IV breast cancer. Recent studies have shown the efficacy of anti-vascular endothelial growth factor drugs on brain tumors, in particular glioblastoma, but none has explored their efficacy and tolerance in breast cancer patients with CNS metastases. We report 4 cases of patients with CNS metastases treated with bevacizumab and paclitaxel. All but 1 had previous whole-brain radiation therapy, performance status 0-2, and radiographic evidence of progressive CNS metastases. Patients received paclitaxel 80 mg/m2 on days 1, 8, and 15, and bevacizumab 10 mg/kg on days 1 and 15. Response was evaluated according to the World Health Organization criteria. Three patients had brain metastases, and 1 had meningeal lesions. Only 1 patient was chemotherapy-naive. Significant antitumor activity was observed, with 1 complete response and 3 partial responses in the CNS metastases. With a mean follow-up of 9 months, duration of response was 11, 10, 8, and 6 months. No patient had extra-CNS progression. This observed antitumor activity suggests efficiency of the combination of bevacizumab and paclitaxel and warrants further evaluation of this combination as an alternative option for the treatment of multiple CNS metastases in breast cancer.
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PMID:Bevacizumab and paclitaxel for breast cancer patients with central nervous system metastases: a case series. 1943 93

Improved molecular understanding of breast cancer in recent years has led to the discovery of important drug targets such as HER-2 and EGFR. Lapatinib is a potent dual inhibitor of HER-2 and EGFR. Preclinical and phase I studies have shown activity with lapatinib in a number of cancers, including breast cancer, and the drug is well tolerated. The main known drug interactions are with paclitaxel and irinotecan. The most significant side-effects of lapatinib are diarrhea and adverse skin events. Rates of cardiotoxicity compare favorably with trastuzumab, a monoclonal antibody against HER-2. This paper focuses on lapatinib in advanced and metastatic breast cancer, which remains an important therapeutic challenge. Phase II and III studies show activity as monotherapy, and in combination with chemotherapy or hormonal agents. Results from these studies suggest that the main benefit from lapatinib is in the HER-2 positive breast cancer population. Combinations of lapatinib and trastuzumab are also being studied and show encouraging results, particularly in trastuzumab-refractory metastatic breast cancer. Lapatinib may have a specific role in treating HER-2 positive CNS metastases. The role of lapatinib as neoadjuvant therapy and in early breast cancer is also being evaluated.
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PMID:Targeted treatment of advanced and metastaticbreast cancer with lapatinib. 2112 49

In recent years, brain metastases have emerged as a main challenge affecting the morbidity and mortality of patients with HER2-positive metastatic breast cancer. In the era following trastuzumab, approximately 30% of these patients develop brain metastases. Trastuzumab does not cross the blood-brain barrier, hence its role is limited to controlling extra-CNS metastases. Lapatinib emerged as a potential candidate; however, its use as a single agent was associated with modest responses. Combination with capecitabine was associated with good results, particularly in patients with newly diagnosed brain metastases. In this article, we discuss the role of trastuzumab and lapatinib in patients with HER2-positive breast cancer with brain metastases. We also highlight the complex structure of the blood-brain barrier and elucidate different potential strategies that could be useful in improving drug delivery.
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PMID:Systemic treatment of brain metastases in HER2-positive breast cancer: current status and future directions. 2233 78

Background. Trastuzumab improves survival in HER2-positive women with metastatic breast cancer (MBC). The consequences of longer survival include a higher likelihood of additional metastases, including those in the central nervous system (CNS). The effect of CNS metastases on both trastuzumab discontinuation and survival in older patients has not been described. Patients and Methods. We used the Surveillance Epidemiology and End Results (SEER) Medicare data to identify a cohort of 562 women age 66 or older with MBC who were diagnosed between January 1, 2000 and December 31, 2005, free of CNS metastases, and initiated trastuzumab after MBC diagnosis. Time to discontinuation and time to death were analyzed using proportional hazards models. Results. Newly diagnosed CNS metastases were associated with both higher risk of trastuzumab discontinuation (relative hazard [RH] = 1.78, 95% CI 1.11-2.87) and higher risk of death (RH = 2.49, 95% CI 1.84-3.37). The incidence rate of new CNS metastases was comparable among various sites of metastasis (10.7 to 14.7 per 1,000 patient-months), except for bone which was higher (24.1 per 1,000). Conclusion. The diagnosis of CNS metastases was associated with an increase in both the likelihood of discontinuing trastuzumab therapy as well as the risk of death.
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PMID:Effect of central nervous system metastases on treatment discontinuation and survival in older women receiving trastuzumab for metastatic breast cancer. 2257 Jun 57


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