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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HER2 (neu, erbB-2), a receptor related to the human epidermal growth factor receptor, has now become more important as a predictive marker of treatment response. While the value and direction of the treatment/HER2 interaction may vary, depending on the agents, dose, or schedule of drug administration, there is little disagreement that HER2 testing is an important part of breast cancer evaluation. In 1998, trastuzumab (Herceptin) was approved for the treatment of HER2-positive metastatic breast cancer patients by the Food and Drug Administration of the USA. Patients with abnormal HER2 in their breast cancer cells (generally 2 or 3+ with the HercepTest, overexpression by other immunohistochemical assays or amplification by fluorescence in situ hybridization [FISH] assay) have demonstrated the greatest response to trastuzumab treatment. It is unclear which test (method, reagent, cut-off points, etc.) is best to use to evaluate HER2 for this purpose because parallel testing of the same cancers from patients who received trastuzumab has only recently been initiated and the data are limited. It is widely believed that breast cancers without HER2 alterations will not be responsive to trastuzumab, although a clinical trial to test this specific hypothesis has not been initiated. There are also concerns that clonal heterogeneity for HER2 within a tumor, or between primary and metastatic cancer foci, may affect treatment response; yet we do not currently evaluate these parameters. Consensus regarding the best methods, reagents, or cut-off points to define HER2 status for determining trastuzumab responsivity has not yet been reached. HER2 testing for other prognostic or predictive purposes, e.g. to determine whether patients are likely to respond to other agents, such as dose-intensive doxorubicin, may be less. Data from the Cancer and Leukemia Group B trial 8541 (companion 8869) suggest that, with proper controls in high-volume laboratories, many of the available methods produce comparable results.
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PMID:HER2--a discussion of testing approaches in the USA. 1152 14

Breast cancer research has developed at a rapid pace over the last decades. Recent discoveries promise to provide individualized treatment options, increased long-term survival for women with breast cancer, and the possibility of moving toward curative intent in the treatment of advanced breast cancer. Age, race, tumor size, histological tumor type, axillary nodal status, standardized pathological grade, and hormone-receptor status are accepted as established prognostic and/or predictive factors for selection of systemic adjuvant treatment of breast cancer. The role of other promising new factors, such as p53 mutations, HER-2 status, plasminogen activator system, histological evidence of vascular invasion, and quantitative parameters of angiogenesis will be determined in ongoing prospective studies. Currently, 5 years' treatment with adjuvant tamoxifen in women with hormone-positive receptor status, is regarded as the optimal duration of treatment. Long-term follow-up on the randomized trials will determine the added benefit of treatment beyond 5 years. Ovarian ablation has shown a reduction in recurrence and death, and the exact role and extent of adjuvant chemotherapy in premenopausal women with hormone-responsive tumors is under discussion. Combination hormonal and chemo-hormonal therapies are also being evaluated. There are no convincing data on the survival impact of tamoxifen as a preventative therapy for breast cancer: longer-term follow-up is required, and the planned meta-analyses in 2005 should help shed light on this issue. Statistically significant benefits have been observed with adjuvant chemotherapy (particularly with anthracycline-containing regimens in premenopausal women) versus no adjuvant chemotherapy. The optimal length of adjuvant anthracycline/cyclophosphamide (AC) regimens needs further evaluation as do randomized comparisons of AC to cyclophosphamide/ doxorubicin/5-fluorouracil (5-FU) and cyclophosphamide/epirubicin/5-FU. Although taxanes promise to provide an additive benefit to adjuvant chemotherapy regimens, the Cancer and Leukemia Group B 9344 and the National Surgical Adjuvant Breast and Bowel Project B-28 studies evaluating paclitaxel in the adjuvant setting have not yet demonstrated statistically significant benefits on disease-free survival and overall survival. In the year 2000, all adjuvant therapy studies conducted by the Co-operative Groups in both node-negative and node-positive disease involve a taxane. High-dose chemotherapy evaluations are still ongoing. The numerous prospective adjuvant therapy trials (hormonal; selective estrogen-receptor modulators; aromatase inhibitors; chemotherapy, involving anthracyclines/taxanes/platinum/trastuzumab; biological factors; elderly women (>70 years); high-risk patients; radiotherapy in 1-3 positive lymph nodes), and neoadjuvant studies might further define the chances to enhance cure rates in the treatment of primary breast cancer.
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PMID:Adjuvant therapy of primary breast cancer: a review of key findings from the 7th international conference, St. Gallen, February 2001. 1152 57

The taxanes paclitaxel and docetaxel represent the most active chemotherapeutic agents developed for the treatment of advanced breast cancer in the last decade, and they are now being incorporated into adjuvant chemotherapy trials for lymph node-positive breast cancer with the hope of improving on the results achieved with CMF (cyclophosphamide, methotrexate, 5-fluorouracil) or anthracycline-based regimens. So far, three randomized paclitaxel-based adjuvant clinical trials enrolling 3170 women (Cancer and Leukemia Group B [CALGB] 9344), 3060 women (National Surgical Adjuvant Project for Breast and Bowel Cancers [NSABP]-B28), and 524 women (M. D. Anderson), respectively, have been reported with respective median follow-up times of 52, 34, and 43 months. This article critically reviews these three studies and gives an overview of the many other randomized clinical trials, due to accrue more than 17 000 women, which are investigating the potential of taxanes in adjuvant breast cancer therapy. Given that the early promise of taxanes suggested by CALGB 9344 is not yet confirmed by the two other trials, only level 2 evidence has been reached to date in regard to a positive contribution of these agents to breast cancer outcome in the adjuvant setting. It is argued that level 1 evidence is highly desirable before adopting taxane-based regimens in standard practice. It is anticipated that a meta-analysis will be needed to comprehensively define the value of taxanes in early breast cancer, and a new model of international collaboration is proposed to find a balance between the need to offer new, more effective therapies to patients as soon as possible and the danger of drawing wrong, premature conclusions regarding the magnitude of benefit of a new regimen.
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PMID:Taxanes in the adjuvant treatment of breast cancer: why not yet? 1177 99

Expression of the multidrug resistance proteins P-glycoprotein, encoded by the MDR1 gene, multidrug resistance-associated protein (MRP1) and the lung resistance-related protein or major vault protein (LRP/MVP) is associated with clinical resistance to chemotherapy in acute myeloid leukemia (AML). Recently, the breast cancer-resistant protein (BCRP), the equivalent of mitoxantrone-resistant protein (MXR) or placental ABC transporter (ABCP), was described in AML. We investigated MDR1, MRP1, LRP/MVP and BCRP mRNA expression simultaneously in 20 paired clinical AML samples from diagnosis and relapse or refractory disease, using quantitative Taqman analysis. In addition, standard assays for P-glycoprotein expression and function were performed. BCRP was the only resistance protein that was expressed at a significantly higher RNA level (median 1.7-fold, P = 0.04) at relapsed/refractory state as compared to diagnosis. In contrast, LRP/MVP mRNA expression decreased as disease evolved (P = 0.02), whereas MDR1 and MRP1 mRNA levels were not different at relapse as compared to diagnosis. Also, at the protein level no difference of MDR1 between diagnosis and relapse was found. A significant co-expression of BCRP and MDR1 was found at diagnosis (r = 0.47, P = 0.04). The present results suggest that BCRP, but not MDR1, MRP1 or LRP/MVP is associated with clinical resistant disease in AML.
Leukemia 2002 May
PMID:Increased expression of the breast cancer resistance protein (BCRP) in relapsed or refractory acute myeloid leukemia (AML). 1198 44

A series of analogs of 1,25-dihydroxyergocalciferol (1-4) was synthesized and screened for their antiproliferative activity in vitro. The structure of new analogs was designed based on biological activity of the previously obtained side-chain modified analogs of vitamin D(2) and D(3). The analogs were obtained by the Julia olefination of C(22)-vitamin D sulfone 11 with side-chain aldehyde 15. The analogs were tested for their antiproliferative activity against the cells of human breast cancer lines T47D and MCF7 as well as human and mouse leukemia lines, HL-60 and WEHI-3, respectively. Analog 2 (PRI-1907) showed the strongest antiproliferative activity out of the present series of analogs of 1,25-dihydroxyvitamin D(2) with the mono homologated and double unsaturated side chain. The activity of 2 was 3-150 times stronger, depending on the cell line, than that of 1,25-dihydroxycholecalciferol (calcitriol), used as standard.
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PMID:Synthesis and antiproliferative activity of side-chain unsaturated and homologated analogs of 1,25-dihydroxyvitamin D(2). (24E)-(1S)-24-Dehydro-24a-homo-1,25-dihydroxyergocalciferol and congeners. 1212 91

Therapy-related myelodysplastic syndrome and acute myelogenous leukemia (t-MDS/AML) are serious complications of chemotherapy and radiotherapy for cancer. High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) may be associated with an increased incidence of these complications. The frequency of t-MDS/AML after ASCT for breast cancer is uncertain. We reviewed our database of 379 consecutive breast cancer ASCT patients treated with alkylator-based chemotherapy, followed for a median of 1.52 years (range 0-8.97), with a median survival of 6.16 years. Three patients have developed tMDS/AML. The probability of developing this complication at 5 years is 0.032 in our series. We have used pathologic, cytogenetic and molecular methods to evaluate which portions of therapy may have predisposed to the development of this complication. Cytogenetic abnormalities were not found in the stem cell harvests of these patients by metaphase analysis or by fluorescence in situ hybridization (FISH). One patient demonstrated a clonal X chromosome inactivation pattern in her stem cell harvest, indicating pre-transplant chemotherapy may have been responsible for the development of her leukemia. As two of our patients developed this complication at greater than 4 years post-transplant, the number of cases may increase with longer follow-up. While the incidence appears to be low, further prospective and retrospective analysis will be necessary to determine which portions of therapy predispose to the development of t-MDS/AML in patients undergoing ASCT for treatment of breast cancer.
Leukemia 2002 Sep
PMID:Therapy-related myelodysplastic syndrome after autologous stem cell transplantation for breast cancer. 1220 Jun 80

The syntheses and antitumor activities of novel 2-amino-4-(3,5,5-trimethyl-2-pyrazolino)-1,3,5-triazine derivatives 4-38 are described. All the compounds prepared were screened at the National Cancer Institute (NCI) for their activities against a panel of 60 tumor cell lines and relationships between structure and antitumor activity in vitro are discussed. The triazines 11, 16, 20, 23, 23 and 34-38 exhibited modest or fairly high activity against one or more human tumor cell lines. Prominent compound with remarkable activity (log GI50, < - 8.00- - 5.00) to all investigated cell lines and highly potent (log GI50 < - 8.00- - 7.64) against some cell lines of Leukemia (CCRF-CEM, K-562, RPMI-8226, SR), CNS Cancer (SF-539) and Breast Cancer (T-47D) was 2-[2-amino-4-(3,5,5-trimethyl-2-pyrazolino)-1,3,5-triazin-6-yl]-3-(5-nitro-2-thienyl)acrylonitrile (25).
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PMID:Synthesis and antitumor activity of novel 2-amino-4-(3,5,5-trimethyl-2-pyrazolino)-1,3,5-triazine derivatives. 1235 Feb 88

The use of systemic adjuvant therapy in women with early-stage breast cancer has been demonstrated to have a profound impact on survival. The role of paclitaxel and docetaxel in the adjuvant setting has attracted a great deal of attention. Both of these agents are highly active in patients with advanced breast cancer. In addition, they can be utilized in combination with anthracyclines, which have been shown to provide a slightly better outcome in patients with early-stage breast cancer compared to non-anthracycline-containing regimens. Randomized trials have demonstrated a potential role for paclitaxel in adjuvant chemotherapy. In the Cancer and Leukemia Group B 9344 trial, which explored the use of doxorubicin and cyclophosphamide with or without paclitaxel, the initial analysis demonstrated a 22% reduction in the relative risk of relapse and a 26% reduction in the relative risk of death in the paclitaxel group. However, a clear role for the use of paclitaxel in adjuvant therapy remains to be defined. The Breast Cancer International Research Group trial 001 compared the combination of docetaxel/doxorubicin/cyclophosphamide to 5-fluorouracil/doxorubicin/cyclophosphamide. This trial demonstrated a promising reduction in the relative risk of recurrence of 32% for the docetaxel/doxorubicin/cyclophosphamide group. Ongoing trials will help to further define the role of taxanes in the adjuvant setting for patients with operable breast cancer.
Clin Breast Cancer 2002 Oct
PMID:Ongoing US cooperative group trials using taxanes in the adjuvant setting. 1243 93

The triplet of docetaxel, doxorubicin, and cyclophosphamide (TAC) has emerged as an alternative chemotherapy regimen for adjuvant management of node-positive breast cancer. Based on recently reported 3-year data from the Breast Cancer International Research Group (BCIRG) 001, disease-free survival was significantly higher in patients who underwent adjuvant chemotherapy with TAC rather than the established regimen of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC). TAC reduced the risk of disease recurrence in estrogen receptor-positive and -negative patients. Whereas overall survival was not significantly different between the two groups, TAC led to a significant reduction in mortality in the subset of patients with one to three involved axillary lymph nodes. Overall, these interim BCIRG 001 results, coupled with those from Cancer and Leukemia Group B-9344 and National Surgical Adjuvant Breast and Bowel Project (NSABP) B-28 (phase III trials of sequential adjuvant chemotherapy with doxorubicin and cyclophosphamide followed by paclitaxel), suggest that taxanes are a valuable component of adjuvant chemotherapy for patients with node-positive breast cancer, including those with estrogen receptor positivity and/or extensive lymph node involvement. Accumulating data in the neoadjuvant setting lend further support to the view that the taxanes confer clinically meaningful benefits in the management of early-stage breast cancer. Such ongoing studies as NSABP B-30 will be instrumental in establishing the relative merits of sequential versus concurrent taxane-anthracycline adjuvant regimens for patients with node-positive breast cancer.
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PMID:Adjuvant therapy approaches to breast cancer: should taxanes be incorporated? 1249 53

The objective of our study was to determine the effect of adding r-metHuSCF to Filgrastim and cyclophosphamide for mobilization of peripheral blood progenitor cells (PBPC), on collection of CD34(+) cells and engraftment after autologous stem cell transplant. Twenty-three patients with previously treated stage II-IV breast cancer received cyclophosphamide (3 g/m(2)), Filgrastim 5 microg/kg daily and r-metHuSCF 20 microg/kg daily. Two PBPC collections were performed on consecutive days starting the day the WBC count was above 7.5 x 10(3)/microl. Collection was performed between days +9 and +12 and the median number of CD34(+) cells collected was 9.9 x 10(6)/kg (1.1-53.1) and 6.6 x 10(6)/kg (1.4-33.8) for the first and second apheresis, respectively. Despite being previously treated patients, the target CD34(+) cell dose required for SCT was obtained in all patients. SCT was associated with rapid neutrophil and platelet engraftment and a highly significant correlation was observed between the number of CD34(+) cells infused and engraftment. Treatment with SCF plus filgrastim was well tolerated, with mild to moderate local skin rash being the most frequently reported adverse event. In conclusion, addition of r-metHuSCF induces mobilization of a large number of CD34(+) cells which results in shortening of time to engraftment and hospitalization.
Leukemia 2003 Feb
PMID:Mobilization of peripheral blood progenitor cells with a combination of cyclophosphamide, r-metHuSCF and filgrastim in patients with breast cancer previously treated with chemotherapy. 1259 44


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