National Cancer Institute®
Last Modified: August 1, 2002
UI - 11398912
AU - Curran M; Wiseman L
TI - Fulvestrant.
SO - Drugs 2001;61(6):807-13; discussion 814
AD - Adis International Limited, Mairangi Bay, Auckland, New Zealand. email@example.com
Fulvestrant is a 7alpha-alkylsulphinyl analogue of estradiol that competes with endogenous estrogen for binding to the estrogen receptor. Once bound to the receptor, fulvestrant attenuates receptor dimerisation, effecting a rapid degradation of the estrogen receptor protein and inhibition of transcription. Fulvestrant is a potent inhibitor of the growth of human breast cancer cells in vitro and in vivo. It has demonstrated pure anti-estrogenic activity in animal systems. Intramuscular fulvestrant 250 mg once a month was as effective as the oral aromatase inhibitor anastrozole 1 mg/day in 2 phase III trials in postmenopausal women with advanced breast cancer who had received prior endocrine therapy. Median time to disease progression (the primary end-point) with fulvestrant and anastrozole was 5.4 and 3.4 months (North American trial) and 5.5 and 5.1 months (European trial). The median duration of response was 19.3 and 10.5 months (North American trial) and 14.3 and 14.0 months (European trial). The most common adverse events with fulvestrant are gastrointestinal disturbances and hot flushes. Fulvestrant showed similar tolerability to anastrozole in 2 phase III trials.
UI - 11505951
AU - Longo F; Mansueto G
TI - [Evolvement of hormone therapy for breast cancer. Florence, March 14, 2001]
SO - Tumori 2001 May-Jun;87(3):A6-14
AD - Oncologia Medica, Policlinico Umberto I, Roma.
UI - 12142395
AU - Schondorf T; Hoopmann M; Warm M; Neumann R; Thomas A; Gohring UJ;
TI - Eisberg C; Mallmann P Serologic concentrations of HER-2/neu in breast cancer patients with visceral metastases receiving trastuzumab therapy predict the clinical course.
SO - Clin Chem 2002 Aug;48(8):1360-2
AD - Department of Gynecology and Obstetrics, University of Cologne, Germany. firstname.lastname@example.org
UI - 12080536
AU - Lynn J
TI - The oncology nurse's role in educating patients on endocrine therapy for metastatic breast cancer--focus on fulvestrant.
SO - Cancer Nurs 2002 Apr;25 Suppl 2():12S-17S
AD - George Washington University Medical Center, Breast Care Center, 901 23rd St NW, Washington, DC 20037, USA.
Fulvestrant, an estrogen receptor downregulator, is an effective and a safe endocrine option for postmenopausal women with advanced breast cancer who progress or develop recurrent disease on prior endocrine therapy. The recommended dose is 250 mg given as a single 5-mL or 2 concurrent 2.5-mL monthly intramuscular injections. Common adverse events associated with fulvestrant are hot flashes, nausea, and mild injection site reactions. Applying warm or cold compresses to the injection site can minimize injection site reactions. In randomized double-blind clinical trials, the frequency of injection site reactions for fulvestrant are no different from the comparator (anastrozole) arm. Overall, fulvestrant has a safety profile similar to aromatase inhibitors. Advantages of this agent are its effectiveness in tamoxifen-resistant tumors and the lack of agonistic property, creating a favorable side-effect profile. One limitation is that there is no evidence regarding the safety and effectiveness of fulvestrant in premenopausal women. Among endocrine therapies used to treat breast cancer, fulvestrant is unique not only in its mechanism of action but also in its mode of administration. With oral therapies, the patient fills the prescription in a pharmacy and takes the medication home. In contrast, with monthly fulvestrant intramuscular injection, the patient will have increased contact with the nurse. The increased interaction between the patient and the nurse will affect the role of nurses providing patient education and monitoring.
UI - 12080537
AU - Lynn J
TI - Estrogen receptor downregulators: new advances in managing advanced breast cancer.
SO - Cancer Nurs 2002 Apr;25 Suppl 2():2S-5S; quiz 18S-19S
AD - George Washington University Medical Center, Breast Care Center, 901 23rd St NW, Washington, DC 20037, USA.
Breast cancer is the most frequently diagnosed malignancy in American women. Although potentially curable in the early stage, metastatic breast cancer, however, is essentially incurable. Because metastatic breast cancer is unlikely to be cured with currently available therapies, the goals of treatment in this setting are prolonging survival and maintaining or improving the quality of life. In patients with receptor (estrogen or progesterone)-positive metastatic breast cancer, endocrine therapy is generally considered the preferred first-line therapy because of the superior tolerability and the similar efficacy when compared with chemotherapy. Today a variety of endocrine therapies are available for the treatment of metastatic breast cancer, among which tamoxifen is the most widely used. Despite its proven efficacy and safety, a significant proportion of patients do not respond to tamoxifen. Further, due to its partial estrogenic activity, tamoxifen is associated with an increased risk of thromboembolism and endometrial cancer. Agents without any estrogenic activity-estrogen receptor downregulators have therefore been developed. Fulvestrant is the first clinically proven agent of this class. Oncology nurses have a key role in managing and educating patients with breast cancer. This supplement provides nurses with an overview of existing and emerging endocrine therapies for postmenopausal patients with metastatic or advanced breast cancer.
UI - 12080538
AU - Dow KH
TI - Existing and emerging endocrine therapies for breast cancer.
SO - Cancer Nurs 2002 Apr;25 Suppl 2():6S-11S
AD - College of Health and Public Affairs, University of Central Florida, HPA 1 Suite 2210, Orlando, FL 32816-2210, USA.
Endocrine therapy is first-line therapy for patients with estrogen receptor-positive or progesterone receptor-positive metastatic breast cancer. Commonly used endocrine therapies are tamoxifen, megestrol acetate, and aromatase inhibitors. Although tamoxifen and megestrol acetate have a favorable therapeutic profile, there are risks associated with these agents. With tamoxifen, the partial agonist property can lead to thromboembolic events. An important adverse event of megestrol acetate is weight gain and fluid retention in some patients. The aromatase inhibitors are currently used as second-line therapy after tamoxifen failure. A recent study showed that anastrozole, an aromatase inhibitor, is as effective or even superior to tamoxifen when used as a first-line therapy. However, not all patients will respond to currently available therapies. A new class of drug, the estrogen receptor downregulators, has been developed. Fulvestrant, the first agent in this new class, not only induces the degradation of the estrogen receptor but also is an estrogen antagonist; further, its lack of agonist activity provides a better safety profile. Two phase III trials have proven that fulvestrant is at least as effective as anastrozole in postmenopausal women with advanced breast cancer. Fulvestrant is an effective and safe endocrine therapy for postmenopausal women who have failed prior endocrine therapy.
UI - 12113239
AU - Nabholtz JM; Reese DM; Lindsay MA; Riva A
TI - Combination chemotherapy for metastatic breast cancer.
SO - Expert Rev Anticancer Ther 2002 Apr;2(2):169-80
AD - University of California, Los Angeles, Peter Ueberroth Building 3360B, 10945 Le Conte Avenue, Los Angeles, CA 90095-7077, USA. email@example.com
Despite more than four decades of effort, the improvement in survival in metastatic breast cancer has been modest. Recently, however, new drugs such as the taxanes have emerged as pivotal agents in the treatment of metastatic disease and they are now being investigated in the adjuvant setting. In addition, the introduction of molecularly targeted therapies such as trastuzumab provides a new paradigm for the development of biologic treatments. The incorporation of trastuzumab into new combination regimens based on potential molecular synergies is a focus of current research.
UI - 12116603
AU - Russell CA
TI - Adjuvant systemic therapy for lymph node-negative breast cancer less than or equal to 1 cm.
SO - Curr Womens Health Rep 2002 Apr;2(2):134-9
AD - Department of Medicine-Oncology, Keck School of Medicine, University of Southern California, NOR 3448, MC 9173, Los Angeles, CA 90089, USA. firstname.lastname@example.org
Routine screening mammography has increased the incidence of stage I breast cancers. Many more women are being diagnosed with lymph node-negative tumors that are less than or equal to 1 cm in greatest diameter. The National Surgical Adjuvant Breast and Bowel Project recently performed a retrospective analysis of 10,302 women participating in one of five clinical trials, including women with lymph node-negative breast cancer. Of these women, 1259 had tumors less than or equal to 1 cm. The analysis of the women with tumors less than or equal to 1 cm revealed an improved relapse-free survival (RFS) if tamoxifen was given after surgery, compared with surgery alone, for women with estrogen receptor (ER)-positive tumors; and for women with ER-negative tumors, RFS was improved by delivering chemotherapy after surgery. The authors suggested that adjuvant systemic therapy should be considered for anyone with an invasive breast cancer, regardless of the size of the tumor. This paper reviews the data presented in that important, historic article, and discusses their conclusions. Also reviewed are the most recent recommendations for treatment of primary breast cancer from the International Consensus Panel that convened at the Seventh International Conference on Adjuvant Therapy of Primary Breast Cancer in St. Gallen, Switzerland. That panel also addressed the issue of adjuvant systemic therapy in women considered to have a minimal or low risk of developing recurrent disease.
UI - 12109640
AU - Hill J; Moore H
TI - Aromatase inhibitors in breast cancer: current and evolving roles.
SO - Cleve Clin J Med 2002 Jul;69(7):561-7
AD - Department of Hematology and Medical Oncology, The Cleveland Clinic Foundation, OH 44195, USA.
The aromatase inhibitors are established first-line drugs for treating metastatic breast cancer in postmenopausal women, and are gaining acceptance as adjuvant treatment as well.
UI - 12118024
AU - Osoba D; Slamon DJ; Burchmore M; Murphy M
TI - Effects on quality of life of combined trastuzumab and chemotherapy in women with metastatic breast cancer.
SO - J Clin Oncol 2002 Jul 15;20(14):3106-13
AD - Quality of Life Consulting, West Vancouver, British Columbia, Canada. email@example.com
PURPOSE: The study was designed to compare the effects of treatment with a combination of trastuzumab (Herceptin; Genentech, Inc, South San Francisco, CA) and chemotherapy versus chemotherapy alone on health-related quality of life (HRQL) in patients with HER-2/neu overexpressing, metastatic breast cancer. PATIENTS AND METHODS: A sample of 400 patients, not previously treated for metastatic disease and randomized to receive either trastuzumab plus chemotherapy (208 patients) or chemotherapy alone (192 patients), completed the European Organization for Research and Treatment Care Quality of Life Questionnaire at baseline and on at least one subsequent occasion at 8, 20, 32, 44, and 56 weeks. HRQL improvement or worsening was defined as a >or= 10-point change (range, 0 to 100 points) in the scores of six preselected domains (global quality of life [QOL], physical, role, social, and emotional functioning, and fatigue). Stable HRQL was defined as a change of less than 10. A Bonferroni correction was applied for multiple testing. RESULTS: After completion of chemotherapy, patients treated with trastuzumab and chemotherapy reported significant improvement in fatigue (P <.05) as compared with their baseline scores. Higher proportions of patients receiving the combined therapy achieved improvement in global QOL (P <.05) than did patients treated with chemotherapy alone. Higher proportions of the combined therapy group also achieved improvement in physical and role functioning and in fatigue as compared with the chemotherapy group, but the differences were not statistically significant. There were no differences in the proportions of patients in the two groups that reported worsening. CONCLUSION: Statistically significantly higher proportions of patients treated with a combination of trastuzumab and chemotherapy reported improved global QOL than did patients treated by chemotherapy alone.
UI - 12118025
AU - Biganzoli L; Cufer T; Bruning P; Coleman R; Duchateau L; Calvert AH;
TI - Gamucci T; Twelves C; Fargeot P; Epelbaum R; Lohrisch C; Piccart MJ Doxorubicin and paclitaxel versus doxorubicin and cyclophosphamide as first-line chemotherapy in metastatic breast cancer: The European Organization for Research and Treatment of Cancer 10961 Multicenter Phase III Trial.
SO - J Clin Oncol 2002 Jul 15;20(14):3114-21
AD - Investigational Drug Branch for Breast Cancer, European Organization for the Research and Treatment of Cancer Data Center, and Jules Bordet Institute, Brussels, Belgium.
PURPOSE: To compare the efficacy and tolerability of the combination of doxorubicin and paclitaxel (AT) with a standard doxorubicin and cyclophosphamide (AC) regimen as first-line chemotherapy for metastatic breast cancer. PATIENTS AND METHODS: Eligible patients were anthracycline-naive and had bidimensionally measurable metastatic breast cancer. Two hundred seventy-five patients were randomly assigned to be treated with AT (doxorubicin 60 mg/m(2) as an intravenous bolus plus paclitaxel 175 mg/m(2) as a 3-hour infusion) or AC (doxorubicin 60 mg/m(2) plus cyclophosphamide 600 mg/m(2)) every 3 weeks for a maximum of six cycles. A paclitaxel (200 mg/m(2)) and cyclophosphamide (750 mg/m(2)) dose escalation was planned at cycle 2 if no grade >or= 3 neutropenia occurred in cycle 1. The primary efficacy end point was progression-free survival (PFS). Secondary end points were response rate (RR), safety, overall survival (OS), and quality of life. RESULTS: A median number of six cycles were delivered in the two treatment arms. The relative dose-intensity and delivered cumulative dose of doxorubicin were lower in the AT arm. Dose escalation was only possible in 17% and 20% of the AT and AC patients, respectively. Median PFS was 6 months in the two treatments arms. RR was 58% versus 54%, and median OS was 20.6 versus 20.5 months in the AT and AC arms, respectively. The AT regimen was characterized by a higher incidence of febrile neutropenia, 32% versus 9% in the AC arm. CONCLUSION: No differences in the efficacy study end points were observed between the two treatment arms. Treatment-related toxicity compromised doxorubicin-delivered dose-intensity in the paclitaxel-based regimen
UI - 12124820
AU - Cocconi G; Di Blasio B; Boni C; Bisagni G; Ceci G; Rondini E; Bella M;
TI - Leonardi F; Savoldi L; Camisa R; Bruzzi P Randomized trial comparing cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) with rotational CMF, epirubicin and vincristine as primary chemotherapy in operable breast carcinoma.
SO - Cancer 2002 Jul 15;95(2):228-35
AD - Medical Oncology Division, Azienda Ospedaliera Universitaria, Parma, Italy. firstname.lastname@example.org
BACKGROUND: According to the overview of Early Breast Cancer Trialists' Collaborative Group, anthracycline containing regimens are superior to cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) as adjuvant chemotherapy for breast carcinoma, but no comparative information is available in terms of primary chemotherapy. In the current randomized controlled trial, the authors compared CMF with a chemotherapy regimen including CMF, epirubicin, and vincristine (CMFEV). METHODS: Two hundred eleven patients with Stages I and II palpable breast carcinoma and tumor diameter > 2.5 cm or < or = 2.5 cm with cytologically proven axillary lymph node involvement were randomized to receive CMF (arm A) or CMFEV regimen (arm B) for four cycles before surgery. After surgery, patients in both arms received adjuvant CMF for three cycles; the postmenopausal patients also received tamoxifen for two years. RESULTS: There were no significant differences in the complete response (CR) and in the CR plus partial response (PR) rates between the two arms. In the subset analysis, among premenopausal patients, significantly higher rates of CR (26% vs 4%, P = 0.004) and of CR + PR rates (80% vs 54%, P = 0.007) were observed in the CMFEV, as compared to the CMF arm. Multivariate analysis confirmed the presence of a significant interaction between menopausal status and type of treatment on the probability of achieving CR (P = 0.02) or CR + PR (P = 0.01). There were no major differences in the side effects of the two treatments, with the exception of more frequent alopecia in the experimental arm. CONCLUSIONS: The results of the current study are in line with those of previous published randomized clinical trials comparing regimens without and with anthracycline as adjuvant treatment, indicating an agreement between the short term response to primary chemotherapy and the long term results observed in the adjuvant setting. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10678
UI - 11843244
AU - Depierre A; Freyer G; Jassem J; Orfeuvre H; Ramlau R; Lemarie E;
TI - Koralewski P; Mauriac L; Breton JL; Delozier T; Trillet-Lenoir V Oral vinorelbine: feasibility and safety profile.
SO - Ann Oncol 2001 Dec;12(12):1677-81
AD - Department of Pneumology, Centre Hospitalier Universitaire Minjoz, Besancon, France.
BACKGROUND: Patient preference as well as concerns and difficulties with intravenous access and pharmaco-economic issues have driven the development of oral vinorelbine. PATIENTS AND METHODS: Four phase II studies were conducted in chemotherapy-naive non-small-cell lung cancer (NSCLC) and as first-line chemotherapy of advanced breast cancer (ABC). As recommended in the phase I dose-finding study, the first step used a weekly dose of 80 mg/m2. This regimen was associated with an excessive rate of early deaths (10%) due to complicated neutropenia and led to discontinuation of the first two studies. In a second step, the dose of 60 mg/m2/week was given for the first three courses and subsequently increased to 80 mg/m2/week, in the absence of severe neutropenia. RESULTS: One hundred and thirty eight patients (76 with NSCLC and 62 with ABC) received this regimen, of whom only five were unable to undergo dose escalation. The incidence of febrile neutropenia and neutropenic sepsis were low (2.9 and 3.6%, respectively). Although severe events were uncommon, nausea/vomiting and diarrhoea were frequent and primary prophylaxis with antiemetics should be recommended. CONCLUSIONS: Overall, the safety profile of oral vinorelbine at 60 mg/m2/week for the first three courses with escalation to 80 mg/m2 is qualitatively comparable to that of i.v. vinorelbine at standard doses. Similarly to i.v. chemotherapy, close haematological monitoring is necessary.
UI - 12029440
AU - Otto AM; Muller CS; Huff T; Hannappel E
TI - Chemotherapeutic drugs change actin skeleton organization and the expression of beta-thymosins in human breast cancer cells.
SO - J Cancer Res Clin Oncol 2002 May;128(5):247-56
AD - Institute of Biochemistry University of Nuremberg-Erlangen, Fahrstr. 17, 91054 Erlangen, Germany. email@example.com
PURPOSE: Elevated expression of the beta-thymosin isotypes T beta(4), T beta(10), and T(15) appears to be involved in the manifestation of a malignant phenotype of human tumor cells, including those of mammary carcinomas. This has evoked an interest in these peptides as diagnostic/prognostic tumor markers. If increased levels of beta-thymosins correspond to tumor malignancy, the question arises whether tumor growth inhibition induced by chemotherapeutic drugs would reduce their expression. METHODS: Two human breast cancer cell lines, the estrogen receptor(ER)-positive MCF-7 and the ER-negative MDA-MB231, were thus analyzed for the amount of beta-thymosin mRNAs by RNase protection assay and for the respective peptide levels by HPLC following different hormonal and drug treatments. RESULTS: Both cell lines, growing in medium with 10% FCS, contain T beta(4) (400-500 fg/cell) and Tbeta(10) (about 100 fg/cell), but no T beta(15). Incubating MCF-7 cells with tamoxifen (1 microM) for 5 days resulted in about 80% growth inhibition and in reduction of intracellular T beta(4) and T beta(10) concentrations by about 40%. Levels of T beta(4) and T beta(10)-mRNA were reduced by about 60%. In contrast, cisplatin (2 microM) changed neither the peptide concentrations nor the mRNA levels of beta-thymosins, in spite of marked growth inhibition. In addition, no changes in beta-thymosin expression were observed in MDA-MB231 cells treated with either drug. MCF-7 cells maintained in estrogen-poor medium (10% horse serum) or stimulated to grow with estradiol (1 nM) had Tbeta(4) and T beta(10) concentrations reduced by about 30%, but changes in T beta(4)- and T beta(10)-mRNA levels did not correspond to those of the peptide. CONCLUSION: Expression of T beta(4) and T beta(10) mRNAs and their peptides is differentially regulated and does not correlate with growth. Instead, reduced beta-thymosin expression may be linked to more intensive TRITC-phalloidin staining of F-actin lining the membrane at sites of intimate cell-cell contacts, while increased beta-thymosin levels appear in cells with more extensive substrate adhesion. This suggests that beta-thymosins play a role in cell surface dynamics.
UI - 12082808
AU - Dimitrievich E; Sterzinger A
TI - Dual breast cancers followed by endometrial cancer.
SO - S D J Med 2002 Jun;55(6):227-9
AD - USD School of Medicine, Sioux Falls, USA.
Two cases in which dual breast cancers occurred at several years interval, followed by endometrial cancer are described. The risk factors for dual breast cancers, the association between breast and endometrial cancer, and the association of tamoxifen therapy with endometrial cancer, and future cancer risk will be briefly discussed.
UI - 12145989
AU - Inaji H; Komoike Y; Motomura K; Kasugai T; Koyama H
TI - [The role of neoadjuvant chemotherapy for breast cancer treatment]
SO - Gan To Kagaku Ryoho 2002 Jul;29(7):1113-9
AD - Dept. of Surgery III, Osaka Medical Center for Cancer and Cardiovascular Diseases.
Neoadjuvant chemotherapy is being used increasingly in the management of patients with breast cancer, especially locally advanced cases. Such treatment is administered with the aim of of reducing the size of the primary tumor to increase the possibility of breast-conserving treatment 86 patients with tumors between 3.1 and 6.0 cm in diameter received epirubicin-based neoadjuvant chemotherapy. There were 55 (64.0%) responders and ultimately 64 patients (74.4%) were treated with BCT. With a median follow-up time of 39 months, 9 patients in the BCT group had developed local recurrence. Long-term follow-up is required to establish whether this procedure is a safe alternative to mastectomy for patients with large breast cancers.
UI - 12145993
AU - Matsui A; Ikeda T; Jinno H; Tajima G; Hohjou T; Tokura H; Mitsui Y;
TI - Asaga S; Muto T; Kitajima M [Developments in endocrine therapy for breast cancer]
SO - Gan To Kagaku Ryoho 2002 Jul;29(7):1138-45
AD - Keio Cancer Center, Keio University Hospital.
After the usefulness of ovariectomy in breast cancer patients was demonstrated, endocrine therapy has been one of the most effective treatments of breast cancer. Thereafter, it became clear that estrogen receptors (ERs) existed in the cells of breast cancer. After it was found that ERs could be used as a predictive factor of endocrine therapy for breast cancer, the validity of endocrine therapy has became more certain. Tamoxifen, a major selective estrogen receptor modulator, is the first agent which has shown evidence of improving survival time and disease-free survival time in the treatment of breast cancer, and is the standard treatment, widely used in the treatment of breast cancer all over the world. LH-RH analogue, commonly used in ablation treatment among premenopausal women, produces the same effect as ovariectomy, and recently has shown good results equivalent to chemotherapy in premenopausal breast cancer treatment. Furthermore, aromatase inhibitors as a form of ablation treatment of postmenopausal women have been used recently. In comparison with tamoxifen, aromatase inhibitors have revealed the same or more effective result in postmenopausal breast cancer treatment. In the near future, endocrine mechanisms in the body and the molecular mechanisms of transcription by ER will be more clearly elucidated, and then new kinds of agent and combined therapies for the endocrine treatment of breast cancer will be developed. Currently, many clinical randomized trials are being conducted to examine the effectiveness of new endocrine treatment. Significant changes are occurring in the endocrine treatment of breast cancer.
UI - 12145994
AU - Tong F; Zhou B; Yang D; Cao Y; Liu P; Liu H; Qiao X; Zhang J
TI - [Clinical evaluation of effects from neo-adjuvant chemotherapy with epirubicin plus paclitaxel in cases of locally advanced breast cancer]
SO - Gan To Kagaku Ryoho 2002 Jul;29(7):1147-52
AD - Dept. of 4th Surgery and Breast Disease Research Center, People's Hospital, Beijing University Medical School.
Neo-adjuvant chemotherapy of epirubicin plus paclitaxel was administered to 23 patients with locally advanced breast cancer (including 13 cases of stage IIb, 6 of stage IIIa, and 4 of stage IIIb). All patients were female. They were treated with epirubicin 60 mg/m2, on day 1, by i.v. followed paclitaxel 150 mg/m2 by 3 hours continuous infusion on day 2 and every 3 weeks repeatedly. Premedication with dexamethasone, ondansetron, diphenhydramine and cimetidine were administered to prevent gastroenteric and allergic reactions before chemotherapy. Two to 4 cycles were used. Ten out of 23 patients had a complete response, 10 had partial response, and 3 had no change. The response rate was 87% (20/23). Six out of 23 patients underwent breast conserving surgery as tumor size had become smaller and downstaging was realized after neo-adjuvant chemotherapy. The major toxicities included neutropenia, myalgia, arthralgia, nephrotoxicity, gastroenteric reactions, alopecia and flushing to the face. However, these were well tolerated in these patients.
UI - 12145999
AU - Miura S; Tominaga T; Koyama H; Nomura Y; Tsuboi M
TI - [Phase I single-dose administration study of exemestane in postmenopausal women]
SO - Gan To Kagaku Ryoho 2002 Jul;29(7):1179-87
AD - Aichi Cancer Center Hospital.
A single-dose administration study of a new type of aromatase inactivator, exemestane, was performed in normal healthy postmenopausal Japanese women. The study was conducted to investigate the safety, effect on serum and urinary estrogen concentrations, and pharmacokinetics of exemestane at 25 or 50 mg. A crossover study using a single dose (25 mg) was also conducted in order to study the effect of meals on these parameters. Adverse events, in which a causal relationship with the study drug could not be excluded, were as follows: hot flushes (2/4), sleepiness (1/4), and glycogeusia (1/4), all of which were mild and transient. There were no clinically significant laboratory test or physical finding abnormalities with either dose, except for one patient in the 50 mg group who had an increase in levels of GPT, ALP and gamma-GTP. Maximal suppression of serum estrogen concentration (22-37% suppression) was achieved 3-4 days after single-dose administration of exemestane (25 mg or 50 mg), and almost no suppression was observed 2 weeks later. A significant decrease in the amount of urinary estrogen excretion occurred on day 4 and day 8 after exemestane administration. The level of urinary estrogen excretion almost returned to baseline levels in the 25 mg group and returned to 65% of baseline levels in the 50 mg group 2 weeks after drug administration. Both serum estrogen concentration and the amount of urinary estrogen excreted decreased in a similar fashion under both fasting and fed conditions, suggesting no effect of meals on the suppression of estrogen concentrations. Exemestane was adsorbed immediately after single-dose administration, and this was followed by a gradual decrease in serum concentrations in a multiphase pattern. An increase in Cmax and AUC0-tz values was observed after meals compared with those values obtained under fasting conditions, yet the increase was not statistically significant, suggesting that the increase was not clinically relevant. The results of this study verified the safety and the estrogen suppressive effects on serum and urinary concentrations of estrogen of a single dose of exemestane up to 50 mg. Furthermore, results suggest that the suppression of serum and urinary estrogen concentrations and pharmacokinetics of exemestane were not affected by food.
UI - 12146001
AU - Tabei T; Ogita M; Hirata K; Satomi S; Kimura M; Abe R; Morishita Y;
TI - Kimura M; Andou J; Higashi Y; Yoshino K; Tominaga K; Kajiwara T; Kitajima M; Koyanagi Y; Watanabe T; Yamaguchi S; Watanabe M; Toyama K; Kanda K; Kashiki Y; Miura S; Kobayashi Z; Aoyama H; Miyazaki I; Oka T; Koyama H; Kinoshita H; Monden M; Takai S; Yayoi E; Kobayashi T; Takatsuka Y; Kajiwara T; Sonoo H; Toge T; Takashima S; Nomura Y; Nagao K; Fujita Y [Early phase II dose-finding study of exemestane in postmenopausal patients with advanced/recurrent breast cancer]
SO - Gan To Kagaku Ryoho 2002 Jul;29(7):1199-209
AD - Saitama Cancer Center.
Exemestane was administered orally to postmenopausal women with advanced/recurrent breast cancer at a dose of 10 mg/day or 25 mg/day once daily for more than 8 weeks in order to evaluate the drug's anti-tumor effects and safety in a dose-finding study. The response rate (CR + PR) in the 10 mg and 25 mg group was 25.0% (8/32) and 31.4% (11/35), respectively, demonstrating no significant differences between the two groups, yet a higher efficacy rate was observed in 25 mg group. The efficacy rate in hormone-treatment-resistant patients within the 10 mg and 25 mg groups was 14.3% (3/21) and 26.1% (6/23), respectively, demonstrating more than a 20% response rate in 25 mg group. Incidences of the adverse events of which relevance to the drug could not be excluded were 30.6% (11/36) in the 10 mg group. 13.9% (5/36) in the 25 mg group and 22.2% (16/72) in the total group. The major adverse events were, hot flashes, numbness of the limbs, nausea, headache etc. Abnormal findings in clinical laboratory tests were as follows: ALP increase; GOT increase; GPT increase; gamma-GTP increase; total cholesterol increase; urinary sediment present. Abnormal findings in endocrine function were as follows: aldosterone decrease; testosterone.cortisol.DHEA-S decrease. But discontinuation due to abnormal laboratory findings was not found. No abnormal findings in physical tests were observed. A significant decrease in plasma estrogen concentration at week 4 was observed in both the 10 mg and 25 mg groups compared with baseline. These low levels were maintained throughout the study period. On the basis of these results, the efficacy of exemestane 25 mg/day was verified to be slightly higher than 10 mg/day. In addition the safety profile had no major adverse events to notice. In these patients with advanced/recurrent breast cancer, 25 mg/day was recommended as the most appropriate dose to be used clinically.
UI - 12146002
AU - Watanabe T; Sano M; Toi M; Saeki T; Kanda K; Miura S; Inaji H; Sono H;
TI - Saeki H; Nishimura R; Fujita Y [Late phase II study of exemestane in postmenopausal patients with breast cancer resistant to anti-estrogenic agents]
SO - Gan To Kagaku Ryoho 2002 Jul;29(7):1211-21
AD - Division of Internal Medicine, National Cancer Center Hospital.
A multi-center trial of exemestane 25 mg, an oral aromatase irreversible inactivator, was conducted to evaluate its efficacy and safety in 33 postmenopausal patients, and to investigate the pharmacokinetics/serum hormone levels in 16 postmenopausal patients, respectively, with breast cancer and anti-estrogen resistance. Exemestane 25 mg was given once daily for up to 48 weeks (maximum). The objective of this study was to confirm the reproducibility of the results shown in two studies in other countries with similar patients, to investigate the possibility of extrapolating the overseas data to Japanese. The response rate (CR + PR) was 24.2% (8.33%), which exceeded the minimum number (6 cases) required to evaluate efficacy. The response rate in this study was very similar to that observed in the two international open studies. Adverse events (subjective/objective symptoms), in which a causal relationship with exemestane administration could not be excluded, were observed in 26 cases (78.8%). Of these, hot flushes, increased sweating, fatigue, and insomnia occurred in more than 10% of patients, which was similar to that observed in the two international open studies. Abnormal laboratory results occurring in more than 10% of patients, in which a causal relationship with exemestane administration could not be excluded, were as follows: lymphocyte count decrease, alkaline phosphate increase, GOT increase, GPT increase, gamma-GTP increase, triglyceride increase, and inorganic phosphate increase, most of which were either grade 1 or 2. A remarkable decrease in serum hormone concentration was observed only for estrogen. The values of AUC0-infinity at day 1 and AUC0-24 h at day 29 (steady state) were similar, suggesting no accumulative effect of exemestane. These results demonstrate the anti-tumor effect and safety of exemestane in postmenopausal anti-estrogen resistant breast cancer patients. The reproducibility of the results of the two foreign studies was verified in Japanese patients, and it is concluded that the foreign trial data on exemestane can be extrapolated to Japanese.
UI - 12146005
AU - Harada T; Hara A; Tsunematsu I; Matsubara C; Izumi N; Iwamoto S; Satake
TI - K [One case of locally advanced breast cancer in which multidisciplinary treatment, chiefly, therapy with preoperative intraarterial infusion of docetaxel (TXT), was successful]
SO - Gan To Kagaku Ryoho 2002 Jul;29(7):1231-4
AD - Dept. of Digestive/General Surgery, Saiseikai-Affiliated Suita Hospital.
We herein report 1 case in which hormone therapy and neoadjuvant chemotherapy by local intraarterial infusion were conducted for locally advanced breast cancer, and were revealed to be useful in terms of local control. Administration of doxifluridine (5'-DFUR: Furtulon) (1,200 mg/day, 5 day continuous dosing followed by 2 day washout) and medroxyprogesterone acetate (MPA: Hysron H) (1,200 mg/day) was followed by chemotherapy consisting of intraarterial infusion of 100 mg of docetaxel (TXT: Taxotere), once monthly, via the left internal thoracic artery and left lateral thoracic artery. As a result, marked shrinkage of tumors was confirmed. Under these circumstances, left standard radical mastectomy plus skin grafting were performed. While under treatment, no serious adverse events were observed, and the patient made satisfactory progress after surgical procedure. She thus left hospital in a positive frame of mind.
UI - 11911507
AU - Jordan C
TI - Historical perspective on hormonal therapy of advanced breast cancer.
SO - Clin Ther 2002;24 Suppl A():A3-16
AD - Robert H. Lurie Comprehensive Cancer Center, Northwestern University School of Medicine, Chicago, Illinois 60611, USA.
BACKGROUND: Endocrine therapy is the preferred first-line therapy in patients with nonaggressive, receptor-positive, metastatic breast cancer. Endocrine therapies in these patients are as effective as chemotherapy in terms of survival and tumor response. In addition, hormonal therapies produce fewer and less severe adverse effects than does chemotherapy. Classes of endocrine therapy currently on the market include selective estrogen receptor modulators (SERMs), aromatase inhibitors, and progestins. For several decades, tamoxifen has been considered the gold standard of therapy. However, despite its proven efficacy, a high proportion of patients do not respond. Therefore, a need exists for alternative therapies or for agents to use following tamoxifen failure. OBJECTIVE: This review article highlights the various endocrine options available for patients with advanced breast cancer and discusses new agents on the horizon. CONCLUSIONS: Although more studies are needed to determine the optimal sequence of hormonal therapy and the ideal agent within each class, the availability of new and multiple options is encouraging for women with advanced breast cancer.
UI - 11911508
AU - Torosian M; O'Shaughnessy J; Parker LM; Vogel C
TI - Fulvestrant: clinical application of an estrogen receptor downregulator.
SO - Clin Ther 2002;24 Suppl A():A31-40
AD - Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA. firstname.lastname@example.org
UI - 11948114
AU - Coon JS; Marcus E; Gupta-Burt S; Seelig S; Jacobson K; Chen S; Renta V;
TI - Fronda G; Preisler HD Amplification and overexpression of topoisomerase IIalpha predict response to anthracycline-based therapy in locally advanced breast cancer.
SO - Clin Cancer Res 2002 Apr;8(4):1061-7
AD - Rush Medical College, Chicago, Illinois 60612, USA. email@example.com
PURPOSE: The putative association between erbB-2 overexpression and favorable response to anthracyline-based therapy in breast cancer is controversial, and the mechanism unclear. We sought to determine whether coamplification and overexpression of the topoisomerase IIalpha gene, near erbB-2 on chromosome 17, and a known anthracycline target, may underlie the association. EXPERIMENTAL DESIGN: Thirty-five patients who had locally advanced breast cancer (LABC) and who had received neoadjuvant, anthracycline-based therapy were studied. Copy number of topoisomerase IIalpha and erbB-2 was determined by fluorescence in situ hybridization, and expression by immunohistochemistry. RESULTS: Of 8 patients with erbB-2 amplification, 5 had a complete response (CR) or minimal residual disease (MRD), 3 had a partial response (PR), and none had stable (StD) or progressive disease (PD) at the time of mastectomy, versus 3 CR or MRD, 16 PR, and 8 StD or PD for patients without amplification (P = 0.008). In contrast, erbB-2 overexpression was not significantly associated with response (P = 0.114). Of 6 patients with topoisomerase IIalpha amplification, 4 had CR or MRD, 2 PR, and none StD or PD, versus 4 CR or MRD, 17 PR, and 8 StD or PD for patients without amplification (P = 0.034). All of the tumors with topoisomerase IIalpha amplification also had erbB-2 amplification, but not vice versa. Overexpression of topoisomerase IIalpha (9 patients) was also associated with favorable response (P = 0.021). CONCLUSIONS: Coamplification of erbB-2 and topoisomerase IIalpha is significantly associated with favorable local response to anthracycline-based therapy in LABC. The expression data favor a plausible mechanism based on topoisomerase IIalpha biology.
UI - 12063069
AU - Holy JM
TI - Curcumin disrupts mitotic spindle structure and induces micronucleation in MCF-7 breast cancer cells.
SO - Mutat Res 2002 Jun 27;518(1):71-84
AD - Department of Anatomy and Cell Biology, UMD School of Medicine, 10 University Drive, Duluth, MN 55812-2487, USA. firstname.lastname@example.org
The dietary phytochemical curcumin possesses anti-inflammatory, -oxidant, and cytostatic properties, and exhibits significant potential as a chemopreventative agent in humans. Although many cell types are arrested in the G2/M-phase of the cell cycle after curcumin treatment, the mechanisms by which this occurs are not well understood. The purpose of this study was to examine the effects of curcumin on the cell cycle of MCF-7 breast cancer cells to determine whether growth arrest is associated with structural changes in cellular organization during mitosis. For this purpose, MCF-7 breast cancer cells were treated with 10-20 microM curcumin, and the effects on cell proliferation and mitosis studied. Structural changes were monitored by immunolabeling cells with antibodies to a number of cytoplasmic and nuclear proteins, including beta-tubulin, NuMA, lamins A/C and B1, lamin B receptor, and centromere antigens. At the concentrations used, a single dose of curcumin does not induce significant apoptosis, but is highly effective in inhibiting cell proliferation for over 6 days. During the first 24-48 h of treatment, many cells are arrested in M-phase, and DNA synthesis is almost completely inhibited. Remarkably, arrested mitotic cells exhibit monopolar spindles, and chromosomes do not undergo normal anaphase movements. After 48 h, most cells eventually leave M-phase, and many form multiple micronuclei instead of individual daughter nuclei. These observations indicate that the curcumin-induced G2/M arrest previously described for MCF-7 cells is due to the assembly of aberrant, monopolar mitotic spindles that are impaired in their ability to segregate chromosomes. The production of cells with extensive micronucleation after curcumin treatment suggests that at least some of the cytostatic effects of this phytochemical are due to its ability to disrupt normal mitosis, and raises the possibility that curcumin may promote genetic instability under some circumstances.
UI - 12113022
AU - Koberle D; Thurlimann B
TI - Anastrozole: pharmacological and clinical profile in postmenopausal women with breast cancer.
SO - Expert Rev Anticancer Ther 2001 Aug;1(2):169-76
AD - Department of Oncology and Hematology, Kantonsspital St. Gallen, Switzerland.
A significant proportion of breast cancers are estrogen-dependent and are therefore amenable to endocrine therapy. Although tamoxifen has been the mainstream of endocrine treatment for over 20 years, new agents have entered the clinic, which have potentially superior activity and an improved safety profile. The development of orally-active, potent and selective third-line aromatase inhibitors represents a major advantage in the management of hormone-sensitive breast cancer. Anastrozole (Arimidex) was the first of these agents to become available and is currently widely indicated for both first- and second-line treatment for postmenopausal women with breast cancer. This review focuses on the biochemical properties and clinical efficacy of anastrozole, providing an overview of the current clinical status and possible future applications.
UI - 12113005
AU - Swords EP
TI - Breast cancer response.
SO - Am J Nurs 2001 Aug;101(8):13; discussion 13-4