National Cancer Institute®
Last Modified: June 1, 2002
UI - 11888004
AU - Lohrisch C; Piccart MJ
TI - Standard medical treatment for early breast cancer.
SO - Eur J Cancer 2001 Oct;37 Suppl 7():S45-58
AD - Institut Jules Bordet, Department of Medicine, Brussels, Belgium.
UI - 11923125
AU - Bland KI
TI - Utilization of sentinel lymph node mapping to determine pathologic outcomes for patients receiving neoadjuvant chemotherapy for locally advanced breast cancer.
SO - Ann Surg Oncol 2002 Apr;9(3):217-9
UI - 11923128
AU - Newman LA; Buzdar AU; Singletary SE; Kuerer HM; Buchholz T; Ames FC;
TI - Ross MI; Hunt KK A prospective trial of preoperative chemotherapy in resectable breast cancer: predictors of breast-conservation therapy feasibility.
SO - Ann Surg Oncol 2002 Apr;9(3):228-34
AD - Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-4009, USA.
BACKGROUND: The role of preoperative chemotherapy for breast cancer is evolving. We initiated a prospective trial of sequential preoperative paclitaxel and doxorubicin-based combination chemotherapy in patients with stage I (tumor >1 cm), II, or IIIA disease and evaluated its effect on breast-conservation therapy (BCT) eligibility. METHODS: Pathology findings for the initial 100 consecutive patients who underwent surgery were analyzed. RESULTS: The median tumor size at presentation was 2.4 cm, and 39% of patients were deemed eligible for BCT. After chemotherapy, the median tumor size decreased to 1.0 cm (P <.001), and 59% of patients seemed BCT eligible (BCT conversion rate 34% among patients initially assessed as BCT ineligible; P <.001). Final pathology confirmed BCT feasibility in 90% of patients assessed as BCT candidates before surgery. The pathology from mastectomy specimens revealed BCT feasibility in 11 (27%) of 41 patients deemed BCT ineligible. Multivariate analysis revealed lobular histology, multicentricity, and calcifications, but not age, initial tumor size, or nodal status to predict final pathology indicating BCT ineligibility. CONCLUSIONS: Induction chemotherapy improves BCT eligibility for breast cancer patients. Improved breast imaging methods after chemotherapy are necessary to improve accuracy in predicting the feasibility of BCT, especially in patients presenting with diffuse calcifications or multicentricity.
UI - 11923129
AU - Stearns V; Ewing CA; Slack R; Penannen MF; Hayes DF; Tsangaris TN
TI - Sentinel lymphadenectomy after neoadjuvant chemotherapy for breast cancer may reliably represent the axilla except for inflammatory breast cancer.
SO - Ann Surg Oncol 2002 Apr;9(3):235-42
AD - Breast Cancer Program, Department of Oncology, Lombardi Cancer Center, Georgetown University School of Medicine, Washington, DC, USA. firstname.lastname@example.org
BACKGROUND: After neoadjuvant chemotherapy, women with locally advanced breast cancer (LABC) undergo a modified radical mastectomy or lumpectomy with axillary lymph node dissection (ALND) and radiotherapy. Sentinel lymphadenectomy (SL) is accepted for axillary evaluation in early breast cancer. We assessed the feasibility and predictive value of SL after neoadjuvant chemotherapy. METHODS: Eligible women received neoadjuvant therapy for LABC and were scheduled to undergo a definitive surgical procedure. Vital blue dye SL was attempted followed by level I and II axillary dissection. RESULTS: SL was successful in 29 of 34 patients (detection rate, 85%). Thirteen patients (45%) had positive nodes, and eight (28%) had negative nodes on both SL and ALND. In five patients (17%), the sentinel node was the only positive node identified. Overall, there was a 90% concordance between SL and ALND. The false-negative rate and negative predictive value were 14% and 73%, respectively. Among the subgroup without inflammatory cancer, the detection and concordance rates were 89% and 96%, respectively. The false-negative rate was 6%, and the negative predictive value was 88%. CONCLUSIONS: SL after neoadjuvant chemotherapy may reliably predict axillary staging except in inflammatory breast cancer. Further studies are required to assess the utility of SL as the only mode of axillary evaluation in these women.
UI - 11923130
AU - Miller AR; Thomason VE; Yeh IT; Alrahwan A; Sharkey FE; Stauffer J; Otto
TI - PM; McKay C; Kahlenberg MS; Phillips WT; Cruz AB Jr Analysis of sentinel lymph node mapping with immediate pathologic review in patients receiving preoperative chemotherapy for breast carcinoma.
SO - Ann Surg Oncol 2002 Apr;9(3):243-7
AD - Division of Surgery, University of Texas Health Science Center at San Antonio, Texas 78229, USA. email@example.com
BACKGROUND: Sentinel lymph node mapping (SLNM) and neoadjuvant chemotherapy are becoming established components of therapy for selected patients with breast carcinoma. However, neoadjuvant therapy has been considered a relative contraindication to SLNM. In an effort to learn whether patients who have received preoperative chemotherapy can undergo accurate SLNM, we evaluated our experience with this technique. METHODS: were concurrently performed in 35 patients who received preoperative chemotherapy. Mapping was performed with (99m)Tc sulfur colloid only in one patient and Lymphazurin dye only in 15 patients, and the two methods were combined in the remainder. RESULTS: SLNM successfully identified a sentinel lymph node in 30 (86%) patients. Metastatic disease was identified in the sentinel lymph nodes of four patients during surgery. The intraoperative pathologic diagnosis proved to be correct in 19 (79%) of 24 patients. The final pathologic diagnosis of the sentinel lymph node reflected the status of the axillary contents in all patients in whom it was identified. CONCLUSIONS: These results demonstrate that SLNM can be consistently performed in patients receiving preoperative chemotherapy for breast cancer, suggesting the utility of this technique in this patient population.
UI - 11993590
AU - Hooper SB; Hill AD; Kennedy S; Dijkstra B; Kelly LM; McDermott EW;
TI - O'Higgins N Tamoxifen as the primary treatment in elderly patients with breast cancer.
SO - Ir J Med Sci 2002 Jan-Mar;171(1):28-30
AD - Department of Surgery, St Vincent's University Hospital, Dublin, Ireland.
BACKGROUND: With the increasing incidence of breast cancer in patients over 70 years, there is interest in the best therapeutic approach. AIMS: To review the management of breast cancer in elderly women and to identify the factors involved in the decision to treat patients with tamoxifen as first line therapy. PATIENTS AND METHODS: Between 1986 and 1999, 302 female patients aged > or = 70 years presented with primary breast cancer, of whom 219 underwent surgery, 79 received tamoxifen as first line treatment and four received primary radiotherapy. A retrospective review was performed on these 79 patients and the outcome recorded. RESULTS: Of these 79 patients, data was available on 68. Follow-up ranged from one to 63 months (median 17 months). Co-morbidity was the principal reason for choosing first line tamoxifen therapy in 61% and patient preference in 11%. Tumour size was less than 5cm in 51%. In 25% tumour size decreased, in 24% it remained stable and in 27% it increased in size following tamoxifen therapy. Additional treatment was prescribed for 33% of patients. CONCLUSION: In the authors' experience, for those elderly patients suffering considerable co-morbidity or who refuse surgical intervention, tamoxifen is an acceptable alternative.
UI - 12011135
AU - Zelek L; Cottu P; Tubiana-Hulin M; Vannetzel JM; Chollet P; Misset JL;
TI - Chouaki N; Marty M; Gamelin E; Culine S; Dieras V; Mackenzie S; Spielmann M Phase II study of oxaliplatin and fluorouracil in taxane- and anthracycline-pretreated breast cancer patients.
SO - J Clin Oncol 2002 May 15;20(10):2551-8
AD - Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France.
PURPOSE: Phase II study evaluating efficacy and safety of combined oxaliplatin/fluorouracil (5-FU) in taxane-pretreated advanced and metastatic breast cancer (ABC) patients. PATIENTS AND METHODS: Sixty-four taxane- and anthracycline-pretreated (within 6 months of study entry) women were treated with oxaliplatin 130 mg/m(2) (2-hour intravenous [IV] infusion), day 1, and 5-FU 1,000 mg/m(2)/d (continuous IV infusion) days 1 to 4, every 3 weeks. RESULTS: Median patient age was 51 years (range, 34 to 71 years), with a median of two involved organs (range, one to six organs), and metastases in the liver (70%), bone (47%), and lung (34%). Patients had a median of two prior chemotherapy regimens (range, one to six regimens), and 78% had previous hormonal therapy, with clinical taxane and anthracycline resistance in 53% and 34%, respectively. A total of 367 cycles were administered, with a median of six cycles/patient (range, one to 15 cycles). Sixty patients were assessable for response (World Health Organization criteria): 17 partial response, 26 stable disease, and 17 disease progression, giving an overall response rate of 27% (95% confidence interval, 16.3% to 39.1%), and 26% and 36% in taxane- and anthracycline-resistant populations, respectively, all responders having metastatic liver disease. Median time to progression was 4.8 months, and median overall survival was 11.9 months. Four treatment-related serious adverse events occurred, seven patients withdrew because of treatment-related toxicity. Hematotoxicity was prevalent but rarely severe, with grade 3-4 neutropenia, leukopenia, and thrombocytopenia in 34%, 19%, and 16% of patients, respectively, and a single episode of febrile neutropenia. One third of patients developed grade 2-3 peripheral neuropathy (oxaliplatin-specific scale), with grade 3 in only 8%. CONCLUSION: This oxaliplatin/5-FU combination is effective with an excellent safety profile in anthracycline/taxane-pretreated ABC patients, showing encouraging activity in patients with anthracycline/taxane-resistance or visceral disease.
UI - 12011136
AU - Love RR; Duc NB; Allred DC; Binh NC; Dinh NV; Kha NN; Thuan TV; Mohsin
TI - SK; Roanh le D; Khang HX; Tran TL; Quy TT; Thuy NV; The PN; Cau TT; Tung ND; Huong DT; Quang le M; Hien NN; Thuong L; Shen TZ; Xin Y; Zhang Q; Havighurst TC; Yang YF; Hillner BE; DeMets DL Oophorectomy and tamoxifen adjuvant therapy in premenopausal Vietnamese and Chinese women with operable breast cancer.
SO - J Clin Oncol 2002 May 15;20(10):2559-66
AD - University of Wisconsin Comprehensive Cancer Center, 610 Walnut Street, Madison, WI 53705-2397, USA. firstname.lastname@example.org
PURPOSE: In 1992, the Early Breast Cancer Trialists' Collaborative Group reported that a meta-analysis of six randomized trials in European and North American women begun from 1948 to 1972 demonstrated disease-free and overall survival benefit from adjuvant ovarian ablation. Approximately 350,000 new cases of breast cancer are diagnosed annually in premenopausal Asian women who have lower levels of estrogen than western women. PATIENTS AND METHODS: From 1993 to 1999, we recruited 709 premenopausal women with operable breast cancer (652 from Vietnam, 47 from China) to a randomized clinical trial of adjuvant oophorectomy and tamoxifen (20 mg orally every day) for 5 years or observation and this combined hormonal treatment on recurrence. At later dates estrogen- and progesterone-receptor protein assays by immunohistochemistry were performed for 470 of the cases (66%). RESULTS: Treatment arms were well balanced. With a median follow-up of 3.6 years, there have been 84 events and 69 deaths in the adjuvant treatment group and 127 events and 91 deaths in the observation group, with 5-year disease-free survival rates of 75% and 58% (P =.0003 unadjusted; P =.0075 adjusted), and overall survival rates of 78% and 70% (P =.041 unadjusted) for the adjuvant and observation groups, respectively. Only patients with hormone receptor-positive tumors benefited from the adjuvant treatment. In Vietnam, for women unselected for hormone receptor status, a cost-effectiveness analysis suggests that this intervention costs $350 per year of life saved. CONCLUSION: Vietnamese and Chinese women with hormone receptor-positive operable breast cancer benefit from adjuvant treatment with surgical oophorectomy and tamoxifen.
UI - 11929341
AU - Goss PE; Strasser K
TI - Tamoxifen resistant and refractory breast cancer: the value of aromatase inhibitors.
SO - Drugs 2002;62(6):957-66
AD - Breast Cancer Prevention Program, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada. email@example.com
Tamoxifen has dominated endocrine treatment of breast cancer for over two decades. It is useful in metastatic breast cancer, adjuvant therapy, preoperative treatment, ductal carcinoma-in-situ and chemoprevention. However, breast cancer may be refractory to tamoxifen or develop resistance to it with ongoing treatment. This resistance involves several mechanisms including receptor mutation causing 'estrogen hypersensitivity' and an increasing agonist effect of tamoxifen. Megestrol (megestrol acetate), in North America, and aminoglutethimide, in Europe, have been the traditional second line therapies after tamoxifen in advanced breast cancer. Aromatase (estrogen synthetase) inhibitors are a logical alternative to tamoxifen to antagonise the effects of estrogen on breast cancer. The third-generation non-steroidal aromatase inhibitors anastrozole, letrozole and vorozole, and the steroidal inhibitor exemestane, have been studied after tamoxifen versus either megestrol or aminoglutethimide. They showed enhanced efficacy and significantly superior toxicity profiles. Compliance with the inhibitors was also significantly better than with the traditional treatments. Aromatase inhibitors have most recently been shown to be superior to tamoxifen as initial therapy and are being extensively tested in the adjuvant setting after, or instead of, tamoxifen. Pilot studies of chemoprevention are also being undertaken. The aromatase inhibitors are an important new addition to the armamentarium of breast cancer therapy.
UI - 12020394
AU - Jones SE
TI - Antiaromatase agents: evolving role in adjuvant therapy.
SO - Clin Breast Cancer 2002 Apr;3(1):33-42
AD - Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX 75246, USA. firstname.lastname@example.org
The goal of adjuvant hormonal therapy is to prevent breast cancer recurrence. Standard therapy with tamoxifen has shown great value in the adjuvant setting; however, its tolerability profile can render it unsuitable for some patients. The aromatase inactivator, exemestane, and the 2 aromatase inhibitors, letrozole and anastrozole, have been shown to be equivalent or superior to tamoxifen with respect to multiple endpoints in patients with metastatic breast cancer. With tolerability profiles that are similar to, and in many cases, more acceptable than that of tamoxifen, and efficacy potentially superior to tamoxifen, studies using the antiaromatase agents as adjuvant therapy are currently ongoing. These trials will answer some important questions, such as the order in which adjuvant hormonal therapies are selected to maximize efficacy, whether the antiaromatase agents show improved tolerability, and whether combination therapy is more effective than monotherapy.
UI - 12020395
AU - Demetri GD; Gabrilove JL; Blasi MV; Hill RJ Jr; Glaspy J
TI - Benefits of epoetin alfa in anemic breast cancer patients receiving chemotherapy.
SO - Clin Breast Cancer 2002 Apr;3(1):45-51
AD - Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA. email@example.com
Breast cancer patients receiving chemotherapy often exhibit anemia, which contributes to symptoms such as fatigue, compromising quality of life (QOL). The present subset analysis assessed the effects of recombinant human erythropoietin (rHuEPO, epoetin alfa) on anemia and QOL in approximately 1300 patients with breast cancer, who were derived from 3 large, community-based clinical trials of epoetin alfa in anemic chemotherapy patients with various malignancies. Epoetin alfa effectively and safely corrected anemia and improved QOL scores on the Linear Analogue Self-Assessment, which measures energy, ability to perform daily activities, and QOL. Clinical, laboratory, and QOL improvements were qualitatively and quantitatively similar to those reported in the larger populations with various tumor types. The efficacy and safety of epoetin alfa did not vary according to dosing frequency (1 vs. 3 times weekly). Epoetin alfa is, therefore, effective and safe in the management of anemia in patients with breast cancer treated with chemotherapy.
UI - 12022477
AU - Pavlov V; Lin PK; Rodilla V
TI - Biochemical effects and growth inhibition in MCF-7 cells caused by novel sulphonamido oxa-polyamine derivatives.
SO - Cell Mol Life Sci 2002 Apr;59(4):715-23
AD - Department of Human and Animal Physiology, Faculty of Biology, University of Sofia St. Kliment Ohridski, Bulgaria.
The novel polyamine derivatives sulphonamido oxa-spermine (oxa-Spm) and sulphonamido oxa-spermidine (oxa-Spd) exhibited rapid cytotoxic action towards MCF-7 human breast cancer cells with IC50 values of 4.35 and 6.47 pM, respectively, after 24-h drug exposure. Neither compound is a substrate of serum amine oxidase. Both oxa-Spm and oxa-Spd caused cell shrinkage, as determined by phase-contrast microscopy. After incubation with 10 microM of either compound for 8 h, the cells underwent chromatin condensation and nuclear fragmentation. However, no clear DNA ladder was obtained by electrophoresis. The sulphonamido oxa-polyamine derivatives and especially oxa-Spd enhanced the activity of polyamine oxidase (PAO), an enzyme capable of oxidising N1-acetylated spermine and spermidine to spermidine and putrescine, respectively, generating cytotoxic H2O2 and 3-acetamidopropanal as by-products. The intracellular polyamine content was only marginally reduced in response to drug treatment. In conclusion, our data show that these novel sulphonamido oxa-polyamine derivatives possess high cytotoxic activity against MCF-7 cells and indicate that induction of PAO may mediate their cytotoxicity via apoptosis.
UI - 11900210
AU - Robertson JF
TI - ICI 182,780 (Fulvestrant)--the first oestrogen receptor down-regulator--current clinical data.
SO - Br J Cancer 2001 Nov;85 Suppl 2():11-4
AD - Department of Surgery, City Hospital Nottingham, UK.
ICI 182,780 (Fulvestrant) is the first in a new class of novel, steroidal, 'pure' antioestrogens--the oestrogen receptor (ER) down-regulators. Its unique mode of action and the absence of partial agonist activity make it a candidate for the treatment of advanced breast cancer in both pre- and postmenopausal women. Tamoxifen has been available for use over the past 25 years. However, its partial agonist activity has been associated with detrimental effects, particularly on the endometrium, and may be associated with the development of tamoxifen resistance. Other antioestrogen agents have previously been unable to demonstrate clinically relevant activity following the development of resistance to tamoxifen. In contrast, the unique mechanism of action of ICI 182,780 results in significant clinical activity in patients failing on tamoxifen therapy. Indeed, phase III clinical trials have demonstrated that ICI 182,780 is at least as effective as the aromatase inhibitor anastrozole in the treatment of postmenopausal patients with advanced disease who have progressed during threatment with prior enocrine therapy. As such, ICI 182,780 will provide a valuable addition to the armamentarium for the treatment of advanced breast cancer.
UI - 11900212
AU - Buzdar AU
TI - Anastrozole (Arimidex)--an aromatase inhibitor for the adjuvant setting?
SO - Br J Cancer 2001 Nov;85 Suppl 2():6-10
AD - Department of Breast Medical Oncology, MD Anderson Cancer Center, University of Texas, Houston 77030, USA.
Anastrozole (Arimidex) is a third-generation aromatase inhibitor which has been shown to possess superior efficacy and tolerability over established endocrine agents in advanced breast cancer. Inhibition of aromatase prevents the conversion of androgen substrates to oestrogen, its sole source in postmenopausal women, thereby leading to regression of hormone-sensitive breast carcinomas. Clinical pharmacology data indicate that anastrozole is a potent aromatase inhibitor, providing near-maximal suppression of serum and intratumoural oestrogens to below detectable levels. Anastrozole may offer greater selectivity compared with other aromatase inhibitors, being without any intrinsic endocrine effects and with no apparent effect on the synthesis of adrenal steroids. It is well tolerated and has a convenient once-daily dosing regimen, ensuring maximum patient compliance. A major clinical programme has demonstrated that anastrozole is superior to the standard endocrine therapy, tamoxifen, for the first-line treatment of postmenopausal women with hormone-sensitive advanced breast cancer. Its superior efficacy in advanced disease, together with its improved tolerability and convenient dosage, make it a suitable agent to be assessed for the treatment of early breast cancer in postmenopausal women. This was investigated in the largest single adjuvant breast cancer study ever to be carried out, the ATAC (Arimidex, tamoxifen, alone or in combination) trial, which has now completed recruitment, with the first efficacy and safety data awaited.
UI - 11972629
AU - Fagnoni FF; Lozza L; Zibera C; Zambelli A; Ponchio L; Gibelli N;
TI - Oliviero B; Pavesi L; Gennari R; Vescovini R; Sansoni P; Da Prada G; Robustelli Della Cuna G T-cell dynamics after high-dose chemotherapy in adults: elucidation of the elusive CD8+ subset reveals multiple homeostatic T-cell compartments with distinct implications for immune competence.
SO - Immunology 2002 May;106(1):27-37
AD - Medical Oncology Division and Surgery Division, Scientific Institute of Pavia, Fondazione Salvatore Maugeri Clinica del Lavoro e della Riabilitazione, IRCCS, Pavia, Italy. firstname.lastname@example.org
Recovery of total T cell numbers after in vivo T-cell depletion in humans is accompanied by complex perturbation within the CD8+ subset. We aimed to elucidate the reconstitution of CD8+ T cells by separate analysis of putative naive CD95- CD28+, memory CD95+ CD28+ and CD28- T cell compartments after acute maximal depletion by high-dose chemotherapy (HD-ChT) in women with high-risk breast cancer. We found that recovery of putative naive CD8+ CD95- CD28+ and CD4+ CD95- CD28+ T cells, was compatible with a thymus-dependent regenerative pathway since their recovery was slow and time-dependent, their values were tightly related to each other, and their reconstitution patterns were inversely related to age. By analysing non-naive T cells, a striking diversion between putative memory T cells and CD28- T cells was found. These latter increased early well beyond normal values, thus playing a pivotal role in total T-cell homeostasis, and contributed to reduce the CD4 : CD8 ratio. In contrast, putative memory T cells returned to values not significantly different from those seen in patients at diagnosis, indicating that this compartment may recover after HD-ChT. At 3-5 years after treatment, naive T cells persisted at low levels, with expansion of CD28- T cells, suggesting that such alterations may extend further. These findings indicate that CD28- T cells were responsible for 'blind' T-cell homeostasis, but support the notion that memory and naive T cells are regulated separately. Given their distinct dynamics, quantitative evaluation of T-cell pools in patients undergoing chemotherapy should take into account separate analysis of naive, memory and CD28- T cells.
UI - 11986765
AU - Talbot DC; Moiseyenko V; Van Belle S; O'Reilly SM; Alba Conejo E;
TI - Ackland S; Eisenberg P; Melnychuk D; Pienkowski T; Burger HU; Laws S; Osterwalder B Randomised, phase II trial comparing oral capecitabine (Xeloda) with paclitaxel in patients with metastatic/advanced breast cancer pretreated with anthracyclines.
SO - Br J Cancer 2002 May 6;86(9):1367-72
AD - Cancer Research UK, Medical Oncology Unit, Churchill Hospital, Oxford OX3 7LJ, UK.
Capecitabine, an oral fluoropyrimidine carbamate, was designed to generate 5-fluorouracil preferentially at the tumour site. This randomised, phase II trial evaluated the efficacy and safety of capecitabine or paclitaxel in patients with anthracycline-pretreated metastatic breast cancer. Outpatients with locally advanced and/or metastatic breast cancer whose disease was unresponsive or resistant to anthracycline therapy were randomised to 3-week cycles of intermittent oral capecitabine (1255 mg m(-2) twice daily, days 1-14, (22 patients)) or a reference arm of i.v. paclitaxel (175 mg m(-2), (20 patients)). Two additional patients were initially randomised to continuous capecitabine 666 mg m(-2) twice daily, but this arm was closed following selection of the intermittent schedule for further development. Overall response rate was 36% (95% CI 17-59%) with capecitabine (including three complete responses) and 26% (95% CI 9-51%) with paclitaxel (no complete responses). Median time to disease progression was similar in the two treatment groups (3.0 months with capecitabine, 3.1 months with paclitaxel), as was overall survival (7.6 and 9.4 months, respectively). Paclitaxel was associated with more alopecia, peripheral neuropathy, myalgia and neutropenia, whereas typical capecitabine-related adverse events were diarrhoea, vomiting and hand-foot syndrome. Twenty-three per cent of capecitabine-treated patients and 16% of paclitaxel-treated patients achieved a > or =10% improvement in Karnofsky Performance Status. Oral capecitabine is active in anthracycline-pretreated advanced/metastatic breast cancer and has a favourable safety profile. Furthermore, capecitabine provides a convenient, patient-orientated therapy. Copyright 2002 Cancer Research UK
UI - 11994976
AU - Falanga A; Toma S; Marchetti M; Palumbo R; Raffo P; Consonni R; Marziali
TI - S; Dastoli G; Barbui T Effect of all-trans-retinoic acid on the hypercoagulable state of patients with breast cancer.
SO - Am J Hematol 2002 May;70(1):9-15
AD - Department of Hematology, Ospedali Riuniti, Largo Barozzi, 14128 Bergamo, Italy. email@example.com
To evaluate whether all-trans-retinoic acid (ATRA) is able to modulate the hemostatic system in patients with solid tumors, we studied patients with locally advanced breast cancer who were enrolled in a Phase Ib study of ATRA +/- Tamoxifen (Tam). In this study, two groups of 15 patients/each were treated for 21 days before operation with ATRA at three doses (15, 45, or 75 mg/m(2)/day on alternate days) given alone (group 1) or in combination with Tam (group 2). One additional group received Tam alone. Plasma samples were evaluated for hypercoagulation markers (FVIIa, F1+2, TAT, D-dimer), fibrinolysis proteins (t-PA, PAI-1), and coagulation inhibitors (protein C, AT). At baseline, cancer patients had FVIIa, F1+2, TAT, and PAI-1 significantly greater than control subjects. During treatment, in the patients given ATRA alone, hypercoagulation markers appeared unmodified. Instead, subjects given Tam alone had a significant elevation of FVIIa, F1+2, and TAT versus baseline. However, in the ATRA + Tam groups, hypercoagulation markers were decreased compared with Tam alone. These results suggest that in selected conditions, pre-operative ATRA may modulate the hypercoagulable state of breast cancer patients. Copyright 2002 Wiley-Liss, Inc.
UI - 12040676
AU - Ishida T; Kusaba T; Hayakawa H
TI - [Incidence of emesis in outpatients on chemotherapy for breast cancer and the clinical efficacy of ondansetron hydrochloride tablets]
SO - Gan To Kagaku Ryoho 2002 May;29(5):723-8
AD - Dept. of Surgery, Takasaki National Hospital.
The incidence of nausea and vomiting was investigated for a maximum of 7 days in 32 breast cancer patients receiving CAF (cyclophosphamide, adriamycin, 5-fluorouracil) and CMF (cyclophosphamide, methotrexate, 5-fluorouracil) therapies. For those patients who experienced nausea and vomiting, 4 mg/day of ondansetron hydrochloride (OND) in tablet form was given in the next course of the chemotherapy, and the anti-emetic effect of the drug was examined. During the observation period, nausea was seen in 17.2-50.0% of the patients and vomiting in 3.1-15.6%. The number of patients who had nausea and vomiting was 22. The anti-emetic effect was examined in 18 out of 22 cases with nausea and vomiting. An anti-emetic effect based on the judgement criterion (efficacy rate) was seen in 94.4% or more of patients for all the days of observation. A marked effect was seen in higher proportion of patients. In conclusion, nausea and vomiting occurred in 17.2-50.0% of the breast cancer patients on chemotherapy (CAF and CMF therapies). To improve the QOL of those patients, anti-emetic treatment using OND tablets as necessary is considered to be effective.
UI - 12040677
AU - Abe R; Tominaga T; Nomizu T; Nomura Y; Takashima S; Koyama H; Sano M;
TI - Tohge T; Ueo H; Ikeda S; Ohashi Y; CGS20267 Study Group [CGS20267 (Letrozole), a new aromatase inhibitor: late phase II study for postmenopausal women with advanced or recurrent breast cancer (no. 1)--investigation of recommended clinical dose CGS20267 Study Group]
SO - Gan To Kagaku Ryoho 2002 May;29(5):729-40
AD - Dept. of Surgery II, Fukushima Medical College.
To determine the recommended clinical dose of CGS20267 (Letrozole), we conducted a randomized comparative study as a late phase II study (first part) in postmenopausal women with advanced or recurrent breast cancer. Forty-one patients were randomly assigned to receive 0.5 mg or 1.0 mg once daily. There were no statistically significant differences in background between the two groups. Although there was no significant difference in the objective response rates between the two groups, the rate was higher at 1.0 mg (44.4%) than at 0.5 mg (38.1%). We also combined these data with the results of an early phase II study. The objective response rates (CR + PR) were 31.4% at 0.5 mg and 42.2% at 1.0 mg, and response rates consisting of CR, PR, and NC for longer than 6 months were significantly higher at a dose of 1.0 mg (68.9%) than 0.5 mg (41.2%). Side effects included drug-related adverse events in 36.8% at 0.5 mg and in 31.6% at 1.0 mg. All of the events were grade 2 or lower, indicating a favorable tolerability of CGS20267. These results demonstrated that CGS20267 1.0 mg once daily is more effective than 0.5 mg, and has comparable safety, in the treatment of postmenopausal women with advanced or recurrent breast cancer. We conclude the recommended clinical dose of CGS20267 should be 1.0 mg once daily.
UI - 12040678
AU - Kimijima I; Tominaga T; Nomizu T; Nomura Y; Takashima S; Koyama H; Sano
TI - M; Tohge T; Ueo H; Ikeda S; Ohashi Y; CGS20267 Study Group [CGS20267 (Letrozole), a new aromatase inhibitor: late phase II study in postmenopausal women with advanced or recurrent breast cancer (no. 2)--evaluation of efficacy and safety at the recommended clinical dose CGS20267 Study Group]
SO - Gan To Kagaku Ryoho 2002 May;29(5):741-9
AD - Dept. of Surgery II, Fukushima Medical College.
In the first part of this late phase II study, we determined the recommended clinical dose of CGS20267 to be 1.0 mg once daily for the treatment of postmenopausal women with advanced or recurrent breast cancer. To further evaluate the efficacy and safety of CGS20267 at the derived or recommended clinical dose, 30 more patients were enrolled in the second part of the study, and were added to the patients treated at 1.0 mg in the first part. As a result of putting the first and second parts together, the objective response rate at 1.0 mg was found to be 38.3%, which was almost equal to that of the early phase II study (40.7%). Drug-related adverse events occurred in 35.4% of the patients at 1.0 mg, and all of the events were of grade 2 or lower. These results demonstrated that CGS20267 1.0 mg once daily is effective and well tolerated in the treatment of postmenopausal women with advanced or recurrent breast cancer.
UI - 12040686
AU - Kusama M; Kaise H; Nakayama S; Ota D; Aoki T; Koyanagi Y; Misaka T;
TI - Matunaga T [A case of breast cancer with multiple bone metastases that responded remarkably to doxifluridine (5'-DFUR), cyclophosphamide (CPA), medroxyprogesterone acetate (MPA) and pamidronate disodium therapy]
SO - Gan To Kagaku Ryoho 2002 May;29(5):785-9
AD - 3rd Dept. of Surgery, Tokyo Medical University.
A 49-year-old female underwent bilateral breast preserving surgery for heterochronic breast cancers. She later developed a sternal metastasis and was recommended for intravenous chemotherapy. However, she refused such an intensive therapy and opted for immunotherapy. Afterward, she came to our hospital because of spinal metastases with back pain. She was treated with oral administration of 5'-DFUR and MPA 1,200 mg/day for 3 weeks, respectively, CPA 100 mg/day for 2 weeks, and pamidronate disodium 30 mg intravenously every 4 weeks. This combined chemotherapy relieved her pain after one course. After 5 courses, tumor markers were reduced to the normal range. After 14 courses, bone X-P revealed that the osteolytic bone showed sclerotic changes and bone scintigraphy showed a complete remission (CR). The adverse effects were not remarkable. This regimen is possible on an outpatient basis, and it may play an important role from the standpoint of treatment effectiveness and the quality of life of the patient.
UI - 12045065
AU - Esmaeli B; Hortobagyi GN; Esteva FJ; Booser D; Ahmadi MA; Rivera E;
TI - Arbuckle R; Delpassand E; Guerra L; Valero V Canalicular stenosis secondary to weekly versus every-3-weeks docetaxel in patients with metastatic breast cancer.
SO - Ophthalmology 2002 Jun;109(6):1188-91
AD - Ophthalmology Section, Department of Plastic Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
PURPOSE: To compare the frequency of canalicular stenosis as a side effect of weekly versus every-3-weeks docetaxel in patients with metastatic breast cancer. DESIGN: Retrospective nonrandomized comparative trial. PATIENTS AND METHODS: Eighteen patients enrolled in a phase II study of weekly docetaxel plus trastuzumab and 18 patients enrolled in a phase II study of every-3-weeks docetaxel plus doxorubicin were evaluated. Each patient underwent a comprehensive ophthalmologic examination, probing and irrigation of the nasolacrimal duct, and, in some instances, a nuclear lacrimal scan. MAIN OUTCOME MEASURES: If epiphora (excessive tearing) was reported by the patient, its time of onset was documented. In patients with epiphora, presence or absence of canalicular stenosis was evaluated on the basis of the findings on probing and irrigation. The duration of treatment with docetaxel, the dose frequency, and the cumulative dose of docetaxel were recorded in each case. RESULTS: Fourteen patients (77%) receiving weekly docetaxel plus trastuzumab had epiphora. Nine of these patients had significant anatomic narrowing of the canaliculi. Bicanalicular silicone intubation or dacryocystorhinostomy was recommended in all nine patients. Eight patients underwent surgery and experienced complete or near complete resolution of epiphora. Although two patients (11%) receiving every-3-weeks docetaxel plus doxorubicin reported transient symptoms of epiphora, neither patient was found to have narrowing of the canaliculi, and the epiphora was not severe enough to justify surgical intervention. The mean duration of docetaxel therapy for the patients in this study was 19 weeks. The mean cumulative dose of docetaxel was higher in patients with canalicular stenosis than in patients without this side effect. CONCLUSIONS: Canalicular stenosis was more common in patients receiving weekly docetaxel than in those receiving every-3-weeks docetaxel for metastatic breast cancer. Bicanalicular silicone intubation early in the course of weekly docetaxel therapy should be considered, because this intervention can prevent complete closure of the canaliculi. Once complete or near complete stenosis of the canaliculi occurs, placement of a permanent Pyrex glass tube may become necessary to overcome the blockage of tear outflow.
UI - 11905711
AU - Smith IE; Lipton L
TI - Preoperative/neoadjuvant medical therapy for early breast cancer.
SO - Lancet Oncol 2001 Sep;2(9):561-70
AD - Breast Unit, Royal Marsden NHS Trust, London, UK. firstname.lastname@example.org
Preoperative (neoadjuvant) medical therapy has emerged over the past decade as a new approach for the treatment of early breast cancer. Results show it has high activity, but survival is no better than with conventional adjuvant treatment. The need for mastectomy is reduced but not abolished; in some studies this effect is associated with a small increase in risk of local recurrence, but without any detriment to survival. Predictive factors for improved outcome include clinical response, and especially pathological complete remissions. However, persisting pathological axillary node involvement is associated with poor outcome. Biological changes in apoptosis or proliferation pathways may prove to be more sensitive surrogate markers than clinical or pathological responses for assessing treatment outcome. The main long-term aim of preoperative medical treatment must be to establish such surrogate predictive markers. This would lead to individualised treatment for each patient, and would allow much more rapid assessment of new drugs than is currently possible with adjuvant therapy trials.
UI - 11905722
AU - Adlard JW; Dodwell DJ
TI - Optimum anthracycline-based chemotherapy for early breast cancer.
SO - Lancet Oncol 2001 Aug;2(8):469-74
AD - Yorkshire Centre for Clinical Oncology, Cookridge Hospital, Leeds, UK. email@example.com
Adjuvant chemotherapy improves the overall survival of women treated after surgery for early breast cancer. Several trials have suggested that anthracycline-containing regimens are more effective than those that do not contain anthracyclines. A modest overall benefit has also been confirmed by the Early Breast Cancer Trialists' Collaborative Group overview. Newer agents, such as the taxanes, are now being tested in the adjuvant setting in randomised trials. The control group of such studies should receive the optimum standard treatment. There are several anthracycline-based regimens in common use, varying in terms of the type of anthracycline used, the dose, and drug scheduling. We review the available evidence and consider whether the optimum anthracycline-containing chemotherapy schedule has now been identified.
UI - 12001113
AU - Vincent-Salomon A; Jouve M; Genin P; Freneaux P; Sigal-Zafrani B; Caly
TI - M; Beuzeboc P; Pouillart P; Sastre-Garau X HER2 status in patients with breast carcinoma is not modified selectively by preoperative chemotherapy and is stable during the metastatic process.
SO - Cancer 2002 Apr 15;94(8):2169-73
AD - Department of Pathology, Institut Curie, Paris, France.
BACKGROUND: The objective of this study was to determine whether HER2 expression levels in breast carcinomas were modified by chemotherapy or during the metastatic process. METHODS: HER2 expression was analyzed on sequential tissue specimens taken from the primary tumor before patients received preoperative chemotherapy (CT) and from post-CT residual breast tumor or at a metastatic site. The first group of patients included 59 women who presented with T2-T4,N1-N2 breast carcinoma and were treated by preoperative anthracycline-based CT and then underwent surgery. The second group included 44 patients with metastatic breast carcinoma localized to the lung (27 patients) or to the liver (17 patients). HER2 status was determined by immunohistochemistry using an anti-p185(HER/neu) monoclonal antibody and was classified as overexpressed or not overexpressed. RESULTS: Among the patients who received preoperative CT, HER2 overexpression was observed in 15 of 59 patients (25%). A complete pathologic response was observed in 2 of these 15 patients. HER2 still was overexpressed in 11 of 13 remaining residual tumors and was no longer detectable in 2 tumors. In addition, the 29 tumors with no HER2 overexpression before CT remained negative after treatment. In patients with metastatic breast carcinoma, HER2 was overexpressed in 11 of 44 primary tumors (25%). In 9 of these 11 tumors, HER2 overexpression was maintained in the metastases (9 pulmonary metastases and 4 hepatic metastases). In two patients who had low levels of HER2 overexpression in their primary tumors, no