National Cancer Institute®
Last Modified: February 1, 2002
UI - 11521785
AU - Icli F; Akbulut H; Dincol D; Onur H; Demirkazik A; Cam R; Cay F; Demirci
TI - S; Uner A; Erekul S A randomized trial of four cycles of adjuvant AC (adriamycin + cyclophosphamide) +/- two cycles of EP (etoposide + cisplatin) in node positive patients with breast cancer.
SO - Ann Oncol 2001 Jul;12(7):1011-3
AD - Department of Medical Oncology, Ibni Sina Hospital, Faculty of Medicine, Ankara University, Sihhiye-Ankara, Turkey. firstname.lastname@example.org
BACKGROUND: Four cycles of AC have been accepted as the standard chemotherapy in breast cancer. In the present randomized study we aimed to assess the efficacy of adjuvant etoposide + cisplatin (EP) combination following four cycles of standard adriamycin + cyclophosphamide (AC) in premenopausal patients with operable breast cancer and axillary lymph node metastasis. PATIENTS AND METHODS: Premenopausal patients with positive axillary lymph nodes following curative modified radical mastectomy were randomized to either four cycles of AC (82 patients) or four cycles of AC + two cycles of EP (83 patients). RESULTS: Median follow-up is 72 months. All randomized and eligible patients are included in the analysis (AC: 80 patients, AC + EP: 78 patients). The five-year disease-free survival (DFS) for the AC + EP group was significantly better when compared to AC group (45.5% vs. 30.4%; P = 0.048). Again, the five-year overall survival (OS) of the whole group was in favor of AC + EP arm, though without statistical significance (68.6% vs. 59.1%; P = 0.247). CONCLUSION: Two cycles of EP following four cycles of AC decreased the relapse rate in operable breast cancer patients.
UI - 11521794
AU - Campone M; Fumoleau P; Delecroix V; Deporte-Fety R; Perrocheau G;
TI - Vernillet L; Borg-Olivier O; Louboutin JP; Bissery MC; Riva A; Azli N Phase I dose-finding and pharmacokinetic study of docetaxel and vinorelbine as first-line chemotherapy for metastatic breast cancer.
SO - Ann Oncol 2001 Jul;12(7):909-18
AD - Centre R Gauducheau, Nantes, France.
BACKGROUND AND PURPOSE: Anthracycline-containing regimens are widely used in advanced breast cancer. However, there is a need for new, non-anthracycline regimens that are active in patients for whom anthracyclines are contraindicated. The aim of this study was to determine the maximum tolerated dose (MTD), the dose-limiting toxicities (DLTs) and recommended doses of docetaxel and vinorelbine as first-line chemotherapy in patients with metastatic breast cancer. The pharmacokinetics of both drugs was also evaluated. PATIENTS AND METHODS: Thirty-four women with first-line metastatic breast cancer were treated with docetaxel, 60-100 mg/m2 (day 1), and vinorelbine, 20-22.5 mg/m2 (days 1 and 5), repeated every three weeks and administered on an outpatient basis. RESULTS: Two MTDs were determined: MTD1 was defined at the dose level using docetaxel 75 mg/m2, and vinorelbine 22.5 mg/m2 DLT being a grade 3 stomatitis that was more related to the dose of vinorelbine than that of docetaxel. Therefore, the study continued with a fixed dose of vinorelbine, 20 mg/m2, and docetaxel 85-100 mg/m2. MTD2 was defined at the dose level combining docetaxel, 100 mg/m2, and vinorelbine, 20 mg/m2; DLTs were grade 3 stomatitis and severe asthenia. Fluid retention was observed in 41% of patients but was never severe or a reason for patient discontinuation. In comparison with historical experience, Daflon 500 did not seem to increase the efficacy of the three-day corticosteroid premedication by further reducing the incidence or severity of fluid retention. No significant neurotoxicity was observed and no patient discontinued the study due to this site effect. Activity was observed at all dose levels and at all metastatic sites, with an overall response rate of 71% (95% CI: 52.0%-85.8%). The median time to progression was 31.4 weeks (95% CI: 12-48 weeks) and median survival was 15.6 months (95% CI: 2.6-26.6 months). The pharmacokinetics of docetaxel and vinorelbine were not modified between day 1 and day 3 when the two drugs were combined with the day 1 administration schedule used in this study. CONCLUSION: The recommended doses for phase II studies are docetaxel, 75 mg/m2 (day 1), plus vinorelbine, 20 mg/m2 (days 1 and 5), repeated every three weeks. At these doses, the combination was found to be active and well tolerated.
UI - 11774205
AU - Hortobagyi GN
TI - Overview of treatment results with trastuzumab (Herceptin) in metastatic breast cancer.
SO - Semin Oncol 2001 Dec;28(6 Suppl 18):43-7
AD - Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4009, USA.
HER2/neu amplification/overexpression confers more aggressive and malignant characteristics on breast cancer cells. Patients with HER2/neu-amplified breast cancer have a worse prognosis than those with normal HER2/neu expression. Over the past decade, the intracellular signaling pathways associated with this growth factor receptor have been elucidated. Multiple therapeutic strategies that target the HER2/neu oncoprotein are under development. Trastuzumab (Herceptin; Genentech, Inc, South San Francisco, CA), a humanized monoclonal antibody that binds to the extracellular domain of the HER2/neu receptor, has undergone phase I, II, and III clinical trials. These studies have shown that, as a single agent, trastuzumab has substantial and reproducible antitumor activity in HER2/neu-amplified metastatic breast cancer. In addition, when added to chemotherapy, trastuzumab improves antitumor efficacy as measured by time to progression, response rate, and survival. Additional chemotherapy/trastuzumab combinations are under active evaluation, and new schedules of administration are being tested. Thus, trastuzumab is the first successful example of molecularly targeted therapy in the management of metastatic breast cancer. Copyright 2001 by W.B. Saunders Company.
UI - 11815957
AU - Harris L; Batist G; Belt R; Rovira D; Navari R; Azarnia N; Welles L;
TI - Winer E; The TLC D-99 Study Group Liposome-encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first-line therapy of metastatic breast carcinoma.
SO - Cancer 2002 Jan 1;94(1):25-36
AD - Duke University Medical Center, Durham, North Carolina, USA. email@example.com
BACKGROUND: The objective of this study was to compare the efficacy and toxicity of the liposome-encapsulated doxorubicin, TLC D-99 (Myocet, Elan Pharmaceuticals, Princeton, NJ), and conventional doxorubicin in first-line treatment of metastatic breast carcinoma (MBC). METHODS: Two hundred twenty-four patients with MBC and no prior therapy for metastatic disease were randomized to receive either TLC D-99 (75 mg/m(2)) or doxorubicin (75 mg/m(2)) every 3 weeks, in the absence of disease progression or unacceptable toxicity. The primary efficacy endpoint was response rate. Responses were assessed using World Health Organization criteria and were required to be of at least 6 weeks' duration. The primary safety endpoint was cardiotoxicity. Cardiac function was monitored by multiple-gated radionuclide cardioangiography scan, and the left ventricular ejection fraction (LVEF) was scored at a central laboratory. Patients were removed from study if LVEF declined 20 or more EF units from baseline to a final value of greater than or equal to 50%, or by 10 or more units to a final value of less than 50%, or onset of clinical congestive heart failure (CHF). RESULTS: Median age was 54 years in both treatment groups. All relevant prognostic factors were balanced, with the exception that there were significantly more progesterone receptor positive patients in the doxorubicin-treated group. Protocol-defined cardiotoxicity was observed in 13% of TLC D-99 patients (including 2 cases of CHF) compared to 29% of doxorubicin patients (including 9 cases of CHF). Median cumulative doxorubicin dose at onset of cardiotoxicity was 785 mg/m(2) for TLC D-99 versus 570 mg/m(2) for doxorubicin (P = 0.0001; hazard ratio, 3.56). The overall response rate was 26% in both treatment groups. The median TTP was 2.9 months on TLC D-99 versus 3.1 months on doxorubicin. Median survival was 16 versus 20 months with a nonsignificant trend in favor of doxorubicin (P = 0.09). Clinical toxicities, commonly associated with doxorubicin, appeared less common with TLC D-99, although the difference was not statistically significant. There was only one report of palmar-plantar erythrodysesthesia (Grade 2) with this liposomal formulation of doxorubicin. CONCLUSIONS: Single-agent TLC D-99 produces less cardiotoxicity than doxorubicin, while providing comparable antitumor activity. Copyright 2002 American Cancer Society.
UI - 11816465
AU - Kitahara S; Ogata H; Katagiri T; Nonaka K; Shiba T
TI - [A 5'-DFUR + CPA + THP therapy that was effective for paclitaxel-refractory pulmonary metastasis of breast cancer--a case report]
SO - Gan To Kagaku Ryoho 2002 Jan;29(1):111-4
AD - Second Dept. of Surgery, School of Medicine, Toho University.
What should be the standard treatment for taxane-refractory metastatic breast cancer remains controversial. In this paper, a case in which the 5'-DFUR + CPA + THP therapy was effective for paclitaxel-refractory metastatic breast cancer is reported. A 41-year-old female received pectoral muscle preserved mastectomy under diagnosis of the left breast found in the left middle lung field with chest X-ray. Paclitaxel 210 mg/m2 (once for three weeks, 8 cycles in total) resulted in marked improvement. The regimen of paclitaxel 70 mg/m2 (medication consecutive once-weekly for three weeks, and withdrawal for next week; 1 cycle) was carried out continuously with the patient ambulatory. Because resistance to the treatment appeared at the time the total dose reached 2,700 mg, 5'-DFUR + CPA + THP therapy (THP 30 mg/m2 (i.v.) x day 1, CPA 77 mg/m2 (p.o.) x 14 days, 5'-DFUR 460 mg/m2 (p.o.) x 14 days; 3 weeks with 1 cycle) was carried out, and definite improvement in the lung findings were observed. 5'-DFUR + CPA + THP therapy may be of use as a second-line therapy in paclitaxel-refractory recurrent breast cancer.
UI - 11816466
AU - Sakuta M; Sumiyama Y; Okamoto Y; Noto Y; Naka I; Kiribayashi T
TI - [A case of locally recurrent breast cancer in which phlebothrombosis of the right leg after hormonal therapy using a high dose of toremifene citrate]
SO - Gan To Kagaku Ryoho 2002 Jan;29(1):115-8
AD - Third Dept. of Surgery, Toho University School of Medicine.
A 72-year-old female had undergone mastectomy at the age of 67 for right breast cancer (T2a, n1 alpha, positive for ER). In the surgery the pectoralis muscle was preserved. For adjuvant therapy, 20 mg/day of tamoxifen was orally administered for 5 years. Six years after surgery, relapse was detected in the right major pectoralis muscle. Irradiation at this site and oral administration of 120 mg/day of toremifene citrate were started. The patient had a medical history of diabetes, and the control of her blood sugar was poor. About 2 months after oral administration of toremifene citrate was started, flares with blebs and swelling were observed in the right lower leg, suggesting acute phlebothrombosis of the right lower limb. The symptoms were ameliorated by intravenous administration of heparin and an antibiotic. In administering a high dose of toremifene citrate to patients with complications, careful follow-up is needed.
UI - 11816478
AU - Kuroi K; Tanaka C; Bando H; Saji S; Hayashi K; Toi M
TI - [Efficacy of biweekly paclitaxel therapy in advanced or recurrent breast cancer]
SO - Gan To Kagaku Ryoho 2002 Jan;29(1):55-60
AD - Dept. of Surgery, Tokyo Metropolitan Komagome Hospital.
To evaluate the feasibility and efficacy of a biweekly schedule of paclitaxel in advanced or recurrent breast cancer, 18 patients were enrolled in this pilot study. Paclitaxel of 120 mg/m2 was administered over 3 hours, and cycles were repeated every two weeks until disease progression or toxicity precluded further treatment. Patients received a median of 10 infusions with actual dose intensity of 55.9 mg/m2/wk, and median time to progression was 4.8 months. The overall response rate was 33.3%, and one patient achieved stable disease for at least 6 months. The responders included patients who received prior anthracycline and/or docetaxel treatment, and the response rate was consistent regardless of metastatic sites. Myelosuppression was the most common toxicity, and a few patients needed G-CSF support, treatment delay or dose reduction because of grade 3 or 4 neutropenia or leukopenia. Although one patient withdrew from this study because of grade 3 sensory disturbance, this regimen was generally well tolerated. A biweekly schedule of paclitaxel seems to be feasible and effective in patients with advanced or recurrent breast cancer.
UI - 11078487
AU - Bonneterre J; Thurlimann B; Robertson JF; Krzakowski M; Mauriac L;
TI - Koralewski P; Vergote I; Webster A; Steinberg M; von Euler M Anastrozole versus tamoxifen as first-line therapy for advanced breast cancer in 668 postmenopausal women: results of the Tamoxifen or Arimidex Randomized Group Efficacy and Tolerability study.
SO - J Clin Oncol 2000 Nov 15;18(22):3748-57
AD - Centre Oscar Lambret, Lille, France. firstname.lastname@example.org
PURPOSE: To compare the efficacy and tolerability of anastrozole (Arimidex; AstraZeneca, Wilmington, DE, and Macclesfield, United Kingdom) with that of tamoxifen as first-line therapy for advanced breast cancer (ABC) in postmenopausal women. PATIENTS AND METHODS: This randomized, double-blind, multicenter study evaluated the efficacy of anastrozole 1 mg once daily relative to tamoxifen 20 mg once daily in patients with tumors that were hormone receptor-positive or of unknown receptor status who were eligible for endocrine therapy. The primary end points were time to progression (TTP), objective response (OR), and tolerability. RESULTS: A total of 668 patients (340 in the anastrozole arm and 328 in the tamoxifen arm) were randomized to treatment and followed-up for a median of 19 months. Median TTP was similar for both treatments (8.2 months in patients who received anastrozole and 8.3 months in patients who received tamoxifen). The tamoxifen:anastrozole hazards ratio was 0.99 (lower one-sided 95% confidence limit, 0.86), demonstrating that anastrozole was at least equivalent to tamoxifen. Anastrozole was also as effective as tamoxifen in terms of OR (32.9% of anastrozole and 32.6% of tamoxifen patients achieved a complete response [CR] or partial response [PR]). Clinical benefit (CR + PR + stabilization of > or = 24 weeks) rates were 56.2% and 55.5% for patients receiving anastrozole and tamoxifen, respectively. Both treatments were well tolerated. However, incidences of thromboembolic events and vaginal bleeding were reported in fewer patients treated with anastrozole than with tamoxifen (4.8% v 7.3% [thromboembolic events] and 1.2% v 2.4% [vaginal bleeding], respectively). CONCLUSION: Anastrozole satisfied the predefined criteria for equivalence to tamoxifen. Together with the lower observed incidence of thromboembolic events and vaginal bleeding, these findings indicate that anastrozole should be considered as first-line therapy for postmenopausal women with ABC.
UI - 11078488
AU - Nabholtz JM; Buzdar A; Pollak M; Harwin W; Burton G; Mangalik A;
TI - Steinberg M; Webster A; von Euler M Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. Arimidex Study Group.
SO - J Clin Oncol 2000 Nov 15;18(22):3758-67
AD - Cancer-Cross Institute, Edmonton, Alberta, Canada. jean-marc.nabholtz@bcom
PURPOSE: The efficacy and tolerability of anastrozole (Arimidex; AstraZeneca, Wilmington, DE, and Macclesfield, United Kingdom) and tamoxifen were compared as first-line therapy for advanced breast cancer in 353 postmenopausal women. PATIENTS AND METHODS: The randomized, double-blind, multicenter study was designed to evaluate anastrozole 1 mg once daily relative to tamoxifen 20 mg once daily in patients with hormone receptor-positive tumors or tumors of unknown receptor status who were eligible for endocrine therapy. Primary end points were objective response (OR), defined as complete (CR) or partial (PR) response, time to progression (TTP), and tolerability. RESULTS: Anastrozole was as effective as tamoxifen in terms of OR (21% v 17% of patients, respectively), with clinical benefit (CR + PR + stabilization > or = 24 weeks) observed in 59% of patients on anastrozole and 46% on tamoxifen (two-sided P =.0098, retrospective analysis). Anastrozole had a significant advantage over tamoxifen in terms of TTP (median TTP of 11.1 and 5.6 months for anastrozole and tamoxifen, respectively; two-sided P =.005). The tamoxifen:anastrozole hazards ratio was 1.44 (lower one-sided 95% confidence limit, 1.16). Both treatments were well tolerated. However, thromboembolic events and vaginal bleeding were reported in fewer patients who received anastrozole compared with those who received tamoxifen (4.1% v 8.2% [thromboembolic events] and 1.2% v 3.8% [vaginal bleeding], respectively). CONCLUSION: Anastrozole satisfied the predefined criteria for equivalence to tamoxifen. Furthermore, we observed both a significant increase in TTP and a lower incidence of thromboembolic events and vaginal bleeding with anastrozole. These findings indicate that anastrozole should be considered as first-line therapy for postmenopausal women with advanced breast cancer.
UI - 11331343
AU - Copur MS; Ledakis P; Bolton M; Norvell M; Muhvic J
TI - Is anastrozole superior to tamoxifen as first-line therapy for advanced breast cancer?
SO - J Clin Oncol 2001 May 1;19(9):2578; discussion 2580-2
UI - 11525361
AU - Le Moal G; Paccalin M; Breux JP; Roblot F; Roblot P; Becq-Giraudon B
TI - Central venous catheter-related infection due to Comamonas testosteroni in a woman with breast cancer.
SO - Scand J Infect Dis 2001;33(8):627-8
AD - Department of Internal Medicine and Infectious Diseases, CHU La Miletrie, Poitiers, France.
A 75-y-old woman with breast cancer presented with bacteremia due to Comamonas testosteroni. Evolution was favorable following adapted antimicrobial therapy and removal of a central venous catheter. This germ seems to be a rare pathogen; as reported in the literature, it is mostly encountered in patients with predisposing factors.
UI - 11464976
AU - Schneeweiss A; Goerner R; Hensel MA; Lauschner I; Sinn P; Kaul S; Egerer
TI - G; Beldermann F; Geberth M; Solomayer E; Grischke EM; Haas R; Ho AD; Bastert G Tandem high-dose chemotherapy in high-risk primary breast cancer: a multivariate analysis and a matched-pair comparison with standard-dose chemotherapy.
SO - Biol Blood Marrow Transplant 2001;7(6):332-42
AD - Department of Gynecology and Obstetrics, University of Heidelberg, Germany. email@example.com
Stem cell-supported high-dose chemotherapy (HDCT) is currently being evaluated in patients with high-risk primary breast cancer (HRPBC), as defined by extensive axillary lymph node involvement. Conclusive results from randomized studies with sufficient patient numbers and follow-up are pending. We retrospectively analyzed 144 HRPBC patients enrolled in a single-arm trial of tandem HDCT at the University of Heidelberg to evaluate the prognostic value of nodal ratio, HER2/neu status, and cytokeratin-positive bone marrow cells and to compare the outcomes of these patients with those of a conventionally treated control group of 91 patients matched by nodal ratio, tumor size, combined hormone-receptor status, and HER2/neu status. The tandem HDCT regimen consisted of 2 cycles of induction chemotherapy followed by 2 cycles of blood stem cell-supported high-dose ifosfamide, 12 g/m2; carboplatin, 900 mg/M2; and epirubicin, 180 mg/m2. Conventionally treated patients received a regimen containing anthracycline without taxanes (52 patients) or CMF (cyclophosphamide, methotrexate, and 5-flurouracil; 39 patients). With a median follow-up of 3.8 years, disease-free, distant disease-free, and overall survival rates were 62%, 65%, and 84%, respectively. In univariate analysis, besides the hormone receptor status (P = .007), HER2/neu overexpression was the strongest predictor of earlier death (P = .017). In multivariate analysis, a nodal ratio of > or =0.8 was found to be the only independent predictor of relapse (relative risk [RR] = 2.09; 95% confidence interval [CI], 1.21-3.60; P = .008) and only the absence of hormone receptors was associated with earlier death (RR = 3.59; 95% CI, 1.45-8.86; P = .006). Despite a trend toward later distant relapse after HDCT compared with standard-dose chemotherapy with a median follow-up of 3 years (P = .059), thus far, matched-pair analysis has not demonstrated significantly better survival rates after HDCT in all matched patients (P = .786) or in the subgroups of anthracycline-treated patients and patients with and without overexpression of HER2/neu. So far, the follow-up time has been too short to draw definite conclusions; however, patients with a nodal ratio of > or =0.8, receptor-negative tumors, or HER2/neu overexpression are at high risk for relapse and death, irrespective of the kind of adjuvant chemotherapy.
UI - 11716446
AU - Tominaga T; Sano M; Nishi T; Sasaki M; Yoshida K; Kimura M; Takashima S;
TI - Asano T; Yoshida M; Fujiwara J; Danno M Postoperative chemoendocrine therapy for women with node-positive stage II breast cancer with combined cyclophosphamide, tamoxifen, and 1-hexylcarbamoyl-5-fluorouracil.
SO - Eur J Surg 2001 Aug;167(8):598-604
AD - Department of Surgery, Tokyo Metropolitan Komagome Hospital, Japan.
OBJECTIVE: To find out whether the addition of 1-hexylcarbamoyl-5-fluorouracil to a postoperative regimen of oral cyclophosphamide and tamoxifen improved the prognosis of carcinoma of the breast. DESIGN: Randomised controlled clinical trial. SETTING: 127 Institutions in Japan. SUBJECTS: 785 Patients with stage II carcinoma (palpable axillary nodes) who had total mastectomy and axillary clearance. INTERVENTIONS: The control group were given oral cyclophosphamide 50 mg/day and tamoxifen 20 mg/day for 2 years; the experimental group were given these drugs plus 1-hexylcarbamoyl-5-fluorouracil 300 mg/day for 2 years. RESULTS: There was no survival advantage (and more toxicity) in the experimental group, except in a subgroup with 1-3 axillary nodes involved. CONCLUSION: The advantage of triple chemotherapy in the subgroup must be substantiated by a new randomised trial confined to patients with 1-3 axillary nodes involved.
UI - 11791116
AU - Bentrem DJ; O'Regan RM; Jordan VC
TI - New strategies for the treatment of breast cancer.
SO - Breast Cancer 2001;8(4):265-74
AD - Department of Surgery, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Medical School, Chicago, IL 60611, USA.
UI - 11791121
AU - Abrams JS
TI - Adjuvant therapy for breast cancer--results from the USA consensus conference.
SO - Breast Cancer 2001;8(4):298-304
AD - Clinical Investigations Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, 6130 Executive Boulevard, EPN 7040, Rockville, MD 20852, USA.
The National Institutes of Health, USA sponsored a Consensus Development Conference on November 1-3, 2000 to review several major questions regarding the adjuvant treatment of breast cancer. A non-governmental group of oncology experts was selected to review clinical trial data and judge the evidence presented by 33 breast cancer researchers. Their conclusions resulted in the following recommendations: (1) Prognostic factors critical for determining risk of recurrence are age, axillary lymph node status, tumor size, histologic type and grade and hormone receptor status. (2) Tamoxifen, administered for 5 years, significantly improves long-term survival for women of all age groups with hormone receptor-positive tumors. Ovarian ablation also prolongs survival in premenopausal women. (3) Multi-agent chemotherapy of 4-6 months duration is associated with an improvement in survival in both hormone receptor-positive and -negative tumors. Anthracycline-containing regimens offer the greatest survival advantage. The role of taxanes is uncertain but they may be useful in selected patients with node-positive tumors. Women with small, node-negative tumors, women over age 70, and those with tumors of favorable histologic subtype (mucinous or tubular) may not require chemotherapy. (4) Adjuvant radiotherapy to the regional lymph nodes and chest wall following mastectomy is indicated for women with 4 or more axillary nodes. (5) Physicians should employ effective visual aids to help them present a complete and balanced view of the absolute benefits versus the side-effects of adjuvant treatments. Important avenues of future research were also discussed and suggestions were made.
UI - 11791122
AU - Nabholtz JM; Reese DM
TI - Third-generation aromatase inhibitors in the treatment of advanced breast cancer.
SO - Breast Cancer 2001;8(4):305-9
AD - Cancer Therapy Development Program and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Peter Ueberroth Building 3360B, 10945 Le Conte Avenue, Los Angeles, CA 90095-7077, USA. firstname.lastname@example.org
UI - 11791123
AU - Tokuda Y; Suzuki Y; Ohta M; Saito Y; Kubota M; Tajima T; Umemura S;
TI - Osamura RY Compassionate use of humanized anti-HER2/neu protein, trastuzumab for metastatic breast cancer in Japan.
SO - Breast Cancer 2001;8(4):310-5
AD - Department of Surgery, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-1193, Japan. email@example.com
The HER-2/neu protein is thought to be a unique and useful target for antibody therapy of cancers overexpressing the HER-2/neu gene. The recombinant humanized anti-HER-2 monoclonal antibody, trastuzumab (Herceptin) was approved for clinical use in the US in 1998. In Japan, it was approved and later became available in June, 2001. We have treated 41 patients with metastatic breast cancer with trastuzumab purchased from the US. In this paper, the details of the patients we experienced are reviewed.
UI - 11791124
AU - Umemura S; Sakamoto G; Sasano H; Tsuda H; Akiyama F; Kurosumi M; Tokuda
TI - Y; Watanabe T; Toi M; Hasegawa T; Osamura RY Evaluation of HER2 status: for the treatment of metastatic breast cancers by humanized anti-HER2 Monoclonal antibody (trastuzumab) (Pathological committee for optimal use of trastuzumab).
SO - Breast Cancer 2001;8(4):316-20
AD - Department of Pathology, Tokai University School of Medicine, Isehara, 259-1193, Japan.
For the treatment of patients with metastatic breast cancer by humanized anti- human epidermal growth factor receptor type 2 (HER2) antibody (trastuzumab), it is important to evaluate HER2 status adequately. "A guideline for HER2 testing" and "HER2 atlas" produced by the "Pathological committee for optimal use of trastuzumab" are introduced in this report. Appropriate evaluations of biological markers are essential for targeting therapy.
UI - 11791125
AU - Gluck S
TI - The worldwide perspective in the adjuvant treatment of primary lymph node positive breast cancer.
SO - Breast Cancer 2001;8(4):321-8
AD - Department of Oncology, University of Calgary, AB, Canada. firstname.lastname@example.org
Adjuvant treatment of early breast cancer has experienced major changes in the last 25 years. Since the mid 1970s when cyclophosphamide, methotrexate and 5-fluorouracil (CMF) resulted in statistically significant and clinically meaningful improvements in disease-free and overall survival, the use of adjuvant chemotherapy has become common practice worldwide. Anthracyclines have long been considered to be among the most active available agents to treat breast cancer and they have become a core component of adjuvant regimens. Anthracycline-containing polychemotherapy regimens provide a significant benefit over CMF. Regimens containing epirubicin are associated with a significant prolongation in relapse-free and overall survival rates compared with standard therapies including CMF. Epirubicin-taxane combinations are highly active in treating metastatic breast cancer and do not appear to be associated with any pharmacokinetic interactions. Epirubicin is a unique anthracycline whose introduction to the US market represents a significant advance in breast cancer treatment. Ongoing research efforts are focusing on combining anthracyclines with taxanes in an effort to continue to improve outcomes following adjuvant therapy.
UI - 11791126
AU - Toi M; Bando H; Saji S
TI - Aromatase and aromatase inhibitors.
SO - Breast Cancer 2001;8(4):329-32
AD - Tokyo Metropolitan Komagome Hospital, 3-18-22, Honkomagome, Bunkyo-ku, Tokyo 113, Japan. email@example.com
Aromatase inhibition provides both paracrine/intracrine and endocrine treatment. Recent accumulated data clarified that 3rd generation aromatase inhibitors potently suppress intratumoral estrogen synthesis particularly in postmenopausal patients. In the 2nd-line treatment for metastatic breast cancer patients, aromatase inhibitors achieved results antitumor activity at least equal to and sometimes better than that of tamoxifen. In the first-line treatment for metastatic breast cancer patients, a recent pivotal study clearly demonstrated that aromatase inhibitor was superior to tamoxifen. Based upon these results, various adjuvant trials which compare aromatase inhibitors with tamoxifen and attempt to determine optimal combination therapies and treatment periods with aromatase inhibitors are currently being conducted. In addition, preliminary studies conducted in neoadjuvant setting indicated that aromatase inhibitors showed an extremely high response rate, which predicts a future paradigm, that neoadjuvant therapy using aromatase inhibitors singly or in combination may become standard for hormone-responsive and post-menopausal breast cancer patients.
UI - 11791127
AU - Kubota T; Furukawa T; Tanino H; Suto A; Otan Y; Watanabe M; Ikeda T;
TI - Kitajima M Resistant mechanisms of anthracyclines--pirarubicin might partly break through the P-glycoprotein-mediated drug-resistance of human breast cancer tissues.
SO - Breast Cancer 2001;8(4):333-8
AD - Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. firstname.lastname@example.org
Juliano and Ling initially reported the expression of a 170 kDa glycoprotein in the membrane of Chinese hamster ovarian cells in 1976, and named this glycoprotein P-glycoprotein (P-gp) based on its predicted role of causing "permeability" of the cell membrane. After much research on anthracycline-resistance, this P-gp was finally characterized as a multidrug-resistant protein coded by the mdr1 gene. Multidrug resistance associated protein (MRP) was initially cloned from H69AR, a human small cell-lung carcinoma cell line which is resistant to doxorubicin (DXR) but does not express P-gp. MRP also excretes substrates through the cell membrane using energy from ATP catabolism. The substrate of MRP is conjugated with glutathione before active efflux from cell membrane. Recently, membrane transporter proteins were re-categorized as members of "ATP-Binding Cassette transporter"(ABC-transporter) superfamily, as shown at http://www.med.rug.nl/mdl/humanabc.htm and http://www.gene.ucl.ac.uk/nomenclature/genefamily/abc.html. A total of ABC transporters have been defined, and MDR1 and multidrug resistance associated protein 1 (MRP1) were reclassified as ABCB1 and ABCC1, respectively. Their associated superfamilies include 11 and 13 other protein, in addition to ABCB and ABCC, respectively. Lung resistance-related protein (LRP) is not a member of the superfamily of ABC transporter proteins, because it shows nuclear membrane expression and transports substrate between nucleus and cytoplasm. LRP was initially cloned from a non-small cell lung carcinoma cell line, SW1573/2R120 which is resistant to DXR, vincristine, etoposide and gramicidin D and does not express P-gp. The mechanisms of resistance remains unclear, and why some resistant cell lines express P-gp and others express MRP and/or LRP is likewise unclear.
UI - 11791128
AU - Heys SD
TI - Evolution of breast cancer management: focus on neoadjuvant chemotherapy.
SO - Breast Cancer 2001;8(4):339-50
AD - Section of Surgical Oncology, Department of Surgery, and the Aberdeen Breast Unit, University Medical Buildings, University of Aberdeen, Foresterhill, Aberdeen AB9 2ZD, Scotland, UK. email@example.com
UI - 11791129
AU - Nakamura S; Kenjo H; Nishio T; Kazama T; Do O; Suzuki K
TI - 3D-MR mammography-guided breast conserving surgery after neoadjuvant chemotherapy: clinical results and future perspectives with reference to FDG-PET.
SO - Breast Cancer 2001;8(4):351-4
AD - Department of Surgery, St. Luke's International Hospital, 9-1 Akashi-cho, Chuo-ku, Tokyo 104-0044, Japan. firstname.lastname@example.org
BACKGROUNDS: Three dimensional MR Mammography (3D-MRM) can detect tumor extension more accurately than mammography or ultrasound. There are two shrinkage patterns observed by 3D-MRM after neoadjuvant chemotherapy. Concentric shrinkage is a good indication for breast conserving surgery. On the other hand, a dendritic pattern was represent ductal spread. Therefore, we developed MRM guided mapping to aid BCS for tumors showing a dendritic pattern. METHODS: Fifteen patients consisting of 8 stage II (T > 3.5 cm) cases and 7 stage IIIa cases aged 39 to 61 years (mean 47-8 years) were treated with AT neoadjuvant chemotherapy with the aim of performing breast conserving surgery. All patients were examined by 3D-MRM before and after neoadjuvant chemotherapy. Breast conserving surgery indications were determined by tumor volume reduction and shrinkage patterns on 3D-MRM. Supine position mapping using MRM was performed for dendritic type tumors. FDG-PET was simultaneously performed for one case with bilateral breast cancer. RESULTS: Breast conserving surgery was performed for 13 of the 15 cases. One case underwent re-operating and mastectomy because of a positive margin. One case had microscopically positive margin and received boost radiation. Therefore, 11 of 15 cases (73.3%) underwent BCS and achieved negative margins under MRM guidance. PET scanning can detect residual tumor and occult metastasis but it is not suitable for mapping because of its spatial resolution. Conclusions: 3D-MRM is a useful modality to select appropriate cases for breast conserving surgery after neoadjuvant chemotherapy. FDG-PET can also detect residual tumor or occult metastasis but it may not be suitable for mapping. Because both examinations have potential, further evaluation of their clinical efficacy is necessary.
UI - 11677975
AU - Pocard M; Vincent-Salomon A; Girodet J; Salmon RJ
TI - Effects of preoperative chemotherapy on liver function tests after hepatectomy.
SO - Hepatogastroenterology 2001 Sep-Oct;48(41):1406-8
AD - Service de Chirurgie Generale et Digestive, Hopital Lariboisiere 2 rue Ambroise Pare, 75475 Paris, France. email@example.com
BACKGROUND/AIMS: Surgical resection of liver metastases is performed increasingly frequently after chemotherapy, which can induce fatty degeneration, possibly modifying the postoperative course after hepatectomy. This study evaluated the effect of chemotherapy on postoperative liver function tests according to the use of preoperative chemotherapy or not. METHODOLOGY: Thirty-two patients were operated on for isolated breast cancer hepatic metastases, after stabilization or complete response to systemic therapy. The first group included 20 patients operated on after chemotherapy (9 major and 11 minor hepatic resections). The second group included 12 patients operated on without chemotherapy (3 major and 9 minor hepatic resections). RESULTS: Histological examination after chemotherapy confirmed micronodular fatty degeneration in 85% of cases, versus none in the control group (P = 0.05). Fall in prothrombin time on day 1 (D1) was more marked in the chemotherapy group (58%) versus control group (74%) (P = 0.001). gamma-glutamyl transpeptidase did not rise on D7 in the chemotherapy group (1.4 x N), even after major hepatectomy (1.6 x N), in contrast with the control group, in which the mean gamma-glutamyl transpeptidase on D7 was 4.6 x N after major hepatectomy and 2 x N after minor hepatectomy (P = 0.05). CONCLUSIONS: Chemotherapy induces almost constant fatty degeneration of the liver. Hepatic regeneration in the postchemotherapy liver is delayed, as reflected by a later and lower elevation of gamma-glutamyl transpeptidase. The predictive risk of liver failure, reflected by prothrombin time, following minor hepatectomy on postchemotherapy liver is similar to that of major hepatectomy to healthy liver.
UI - 11693900
AU - Buchholz TA; Hill BS; Tucker SL; Frye DK; Kuerer HM; Buzdar AU; McNeese
TI - MD; Singletary SE; Ueno NT; Pusztai L; Valero V; Hortobagyi GN Factors predictive of outcome in patients with breast cancer refractory to neoadjuvant chemotherapy.
SO - Cancer J 2001 Sep-Oct;7(5):413-20
AD - Department of Radiation Oncology,The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
PURPOSE: The purpose of this study was to determine the clinical, pathological, and treatment factors that are predictive of local-regional recurrence and overall survival for patients with breast cancer that is refractory to neoadjuvant chemotherapy. PATIENTS AND METHODS: This study analyzed the data of the 177 breast cancer patients treated on our institutional protocols who had less than a partial response to neoadjuvant chemotherapy. The initial clinical stage of disease was II in 27%, III in 69%, and IV (supraclavicular lymph node involvement) in 4%. Surgery was performed in 94% of the patients, and 77% of these patients also received adjuvant chemotherapy. RESULTS: After a median follow-up of 5.2 years, 106 patients experienced disease recurrence, with 98 of these having distant metastases and 45 having local-regional recurrence. The 5- and 10-year overall survivals for the entire group were 56% and 33%, respectively. The factors that were independently associated with a statistically significant poorer overall survival in a Cox regression analysis were pathologically involved lymph nodes after surgery, estrogen receptor-negative disease, and progressive disease during neoadjuvant chemotherapy. The 5-year overall survival for patients with pathologically negative lymph nodes ranged from 84% (estrogen receptor-positive disease) to 75% (estrogen re-ceptor-negative disease), compared with rates for patients with pathologically positive lymph nodes of 66% (estrogen receptor-positive disease) and 40% (estrogen receptor-negative disease). The 5-year survival of patients with progressive disease was only 19%. The 5- and 10-year local-regional recurrence rates for the 177 patients were 27% and 34%, respectively. Significant factors on Cox analysis that predicted for local-regional recurrence were four or more pathologically involved lymph nodes and estrogen receptor-negative disease. For the 105 patients treated with surgery and postoperative radiation therapy, the 10-year local-regional recurrence rates for the subgroups with 0, 1, or 2 of these factors were 12%, 25%, and 44%, respectively. CONCLUSIONS: For patients with a poor response to neoadjuvant chemotherapy, conventional treatments achieve reasonable outcomes in those with lymph node-negative disease or estrogen receptor-positive disease. However, more active systemic and local therapies are needed for patients with estrogen receptor-negative disease and positive lymph nodes and for those with clinical evidence of progressive disease during neoadjuvant chemotherapy.
UI - 11782394
AU - Crawford KW; Bowen WD
TI - Sigma-2 receptor agonists activate a novel apoptotic pathway and potentiate antineoplastic drugs in breast tumor cell lines.
SO - Cancer Res 2002 Jan 1;62(1):313-22
AD - Howard University College of Medicine, Department of Pharmacology, Washington, DC 20059, USA.
We have reported previously that sigma-2 receptors are expressed in high densities in a variety of tumor cell types (B. J. Vilner et al., Cancer Res., 55: 408-413, 1995) and that various sigma ligands have cytotoxic effects (B. J. Vilner et al., J. Neurosci., 15: 117-134, 1995). Other investigators have demonstrated increased expression of sigma-2 receptors in rapidly proliferating tumors (R. H. Mach et al., Cancer Res., 57: 156-161, 1997) and the ability of some sigma ligands to inhibit proliferation (P. J. Brent and G. T. Pang, Eur. J. Pharmacol., 278: 151-160, 1995). We demonstrate here the ability of sigma-2 receptor agonists to induce cell death by a mechanism consistent with apoptosis. In breast tumor cell lines that are sensitive (MCF-7) and resistant (MCF-7/Adr-, T47D, and SKBr3) to antineoplastic agents, incubation with the sigma-2 subtype-selective agonists CB-64D and CB-184 produced dose-dependent cytotoxicity (measured by lactate dehydrogenase release into medium). The EC(50) for this response was similar across cell lines, irrespective of p53 genotype and drug-resistance phenotype. CB-64D and the subtype nonselective sigma-2 agonists haloperidol and reduced haloperidol induced terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining in MCF-7 and T47D cells, indicating that cell death occurs via apoptosis. Apoptosis was also indicated by increases in Annexin V binding caused by CB-64D. In MCF-7 cells, cytotoxicity and Annexin V binding induced by the antineoplastics doxorubicin and actinomycin D was partially or completely abrogated by certain specific and general inhibitors of caspases. In contrast, caspase inhibitors had no effect on sigma-2 receptor-mediated (CB-64D and CB-184) cytotoxicity or Annexin V binding. Marked potentiation of cytotoxicity was observed when a subtoxic dose of CB-184 was combined with doxorubicin or actinomycin D, both in drug-sensitive (MCF-7) and drug-resistant (MCF-7/Adr-) cell lines. Haloperidol potentiated doxorubicin only in drug-resistant cells. These findings suggest the involvement of a novel p53- and caspase-independent apoptotic pathway used by sigma-2 receptors, which is distinct from mechanisms used by some DNA-damaging, antineoplastic agents and other apoptotic stimuli. These observations further suggest that sigma-2 receptors may be targets that can be therapeutically exploited in the treatment of both drug-sensitive and drug-resistant metastatic tumors.
UI - 11718178
AU - Anonymous
TI - Exemestane: new preparation. No tangible advance in metastatic breast cancer after tamoxifen failure.
SO - Prescrire Int 2001 Aug;10(54):108-9
(1) The reference second-line hormone treatment for breast cancer in postmenopausal women, after failure of anti-oestrogen therapy, is an