National Cancer Institute®
Last Modified: September 1, 2002
UI - 11856590
AU - Viens P; Maraninchi D
TI - High-dose chemotherapy in advanced breast cancer.
SO - Crit Rev Oncol Hematol 2002 Feb;41(2):141-9
AD - Department of Medicine, Institut Paoli Calmettes, Marseille, France. firstname.lastname@example.org
Based on in vitro and animals studies which assess dose effect relationship specially for alkylating agent, and on the importance on dose intensity in human protocols, high-dose chemotherapy with stem cell support has been widely evaluated in various tumours, particularly in breast cancer. Moreover, in the last few years, the utilization of hematopoietic growth factors and peripheral stem cells has permitted a large diffusion of this approach. However, there is not yet clear data on the place of such a treatment in breast cancer. Few randomized trials are available, with mature data. Only one shows an advantage for high-dose therapy in metastatic disease. In adjuvant setting, sample sizes are too small or follow-up not long enough to draw any definitive conclusion on the place of high-dose consolidation chemotherapy in breast cancer. In inflammatory breast cancer, which is a much more less frequent disease, encouraging results have been published in phase two studies, looking at pathological response, or in pilot studies. The next few years will give a mature date of randomized trials which evaluate high-dose chemotherapy given after conventional treatment in metastatic or high risk disease. Effort should be done to better evaluate this strategy in terms of cost and quality of life and to design new studies aimed to evaluate front line multiple intensification.
UI - 12138378
AU - Anonymous
TI - Fulvestrant (faslodex) for advanced breast cancer.
SO - Med Lett Drugs Ther 2002 Jul 22;44(1135):65-6
UI - 12161606
AU - Chappuis PO; Goffin J; Wong N; Perret C; Ghadirian P; Tonin PN; Foulkes
TI - WD A significant response to neoadjuvant chemotherapy in BRCA1/2 related breast cancer.
SO - J Med Genet 2002 Aug;39(8):608-10
UI - 11858901
AU - Kaleli S; Calay Z; Altinok T; Kosebay D
TI - Endometrial mixed Mullerian tumor with heterologous elements following tamoxifen therapy for breast cancer: a case report and literature review.
SO - Eur J Obstet Gynecol Reprod Biol 2002 Mar 10;101(2):204-8
AD - Department of Obstetrics and Gynecology, Cerrahpasa Medical School, Istanbul University, P.O. Box 11, Cerrahpasa, 34000, Istanbul, Turkey. email@example.com
CASE: A 67-year-old multiparous woman received 20mg tamoxifen daily for four years after surgical treatment of breast cancer. She presented with vaginal bleeding. Uterine curettage revealed a uterine MMT with heterologous elements. She was treated surgically with adjuvant radiotherapy. Tumor cells were found to be estrogen receptor negative and progesterone receptor positive. Uterine MMT may be linked to long term use of tamoxifen. A mechanism in developing MMT other than estrogen receptor pathway may be possible.
UI - 11900315
AU - Cunnick GH; Mokbel K
TI - Aromatase inhibitors.
SO - Curr Med Res Opin 2001;17(3):217-22
AD - St George's Breast Cancer Centre, St George's Hospital, London, UK.
The new non-steroidal and steroidal aromatase inhibitors are at least as effective as megestrol acetate (MA) as second-line hormonal agents in postmenopausal women with breast cancer. However, they are superior to MA in terms of tolerability and adverse effects. Letrozole and exemestane have been shown to be superior to MA in terms of efficacy. Furthermore, exemestane and anastrozole demonstrated a survival advantage over MA. These drugs are therefore considered established second-line hormonal agents. There is a growing body of evidence supporting the role of third-generation aromatase inhibitors as first-line therapy for ER-and/or PgR-positive advanced breast cancer in postmenopausal women, and as a neoadjuvant therapy in postmenopausal women with hormone receptor positive tumours unsuitable for breast conserving surgery. Studies comparing these drugs head-to-head and with adjuvant tamoxifen are currently in progress. The potential role of these drugs in breast cancer prevention is worth investigating.
UI - 11996638
AU - Shaw HS; Ellis MJ
TI - Letrozole in the treatment of breast cancer.
SO - Expert Opin Pharmacother 2002 May;3(5):607-17
AD - Multidisciplinary Breast Program, Duke University Medical Center, Box 3381, Durham, NC 27710, USA. firstname.lastname@example.org
Over the last 30 years the role of tamoxifen in breast cancer treatment has been progressively expanded by clinical investigation to encompass the entire spectrum of disease from cancer chemoprevention to palliation of advanced disease. The primacy of tamoxifen for these indications in postmenopausal women is now under challenge by the selective aromatase inhibitors, a class of endocrine agent that induces oestrogen deprivation rather than oestrogen receptor blockade. This review considers the biochemical, pharmacological and clinical properties of the nonsteroidal aromatase inhibitor letrozole. This agent is superior to tamoxifen for the treatment of metastatic breast cancer, a finding that suggests that letrozole may ultimately eclipse tamoxifen for other indications, including chemoprevention. Further clinical investigation will be necessary to establish the risks and benefits of letrozole versus tamoxifen for each new indication, with adjuvant therapy being the next in line. The object of this review is to provide a reference source on the biochemical, pharmacological and clinical properties of letrozole for clinicians to consider both established and future indications.
UI - 12072036
AU - Kiesel LA; Rody A; Greb RR; Szilagyi A
TI - Clinical use of GnRH analogues.
SO - Clin Endocrinol (Oxf) 2002 Jun;56(6):677-87
AD - Department of Obstetrics and Gynaecology, University of Muenster, Germany. email@example.com
UI - 12095537
AU - Pavlov V; Rodilla V; Kong Thoo Lin P
TI - Growth, morphological and biochemical changes in oxa-spermine derivative-treated MCF-7 human breast cancer cells.
SO - Life Sci 2002 Jul 26;71(10):1161-73
AD - Department of Human and Animal Physiology, Faculty of Biology, University of Sofia St. Kliment Ohridski, Dr. Tzankov Blvd. 8, 1164 Sofia, Bulgaria. firstname.lastname@example.org
The growth inhibitory properties of two oxa-spermine derivatives named compound 1 and compound 2, representatives of a novel type of polyamine derivatives, were studied. Dose-response growth inhibitory curves obtained after 48h drug exposure demonstrated the much higher cytotoxic activity of compound 1 towards MCF-7 human breast cancer cells. Further experiments with compound 1 showed that this oxa-spermine derivative exhibited considerable cytotoxicity with IC(50) values of 3.74 microM and 2.93 microM after 24h and 48h drug exposure respectively. In MCF-7 cells, after 8h drug (10 microM) exposure it caused shrinkage, chromatin condensation and nuclear fragmentation. However, no clear DNA laddering was detected in treated cells. Drug treatment provoked an increase in polyamine oxidase (PAO) activity. This enzyme is able to produce cytotoxic H(2)O(2) and 3-acetamidopropanal, catalyzing the oxidative deamination of N(1)-acetylated derivatives of spermine and spermidine to spermidine and putrescine respectively. Taken together these data demonstrate that the novel oxa-polyamine derivative compound 1 has considerable cytotoxic activity towards MCF-7 cells and indicate that an induction of PAO may be involved in its cytotoxic and apoptotic effects.
UI - 12137722
AU - Lewis R; Bagnall AM; Forbes C; Shirran E; Duffy S; Kleijnen J; Riemsma
TI - R; ter Riet G The clinical effectiveness of trastuzumab for breast cancer: a systematic review.
SO - Health Technol Assess 2002;6(13):1-71
AD - NHS Centre for Reviews and Dissemination, University of York, UK.
UI - 12121832
AU - Harries M; Smith I
TI - The development and clinical use of trastuzumab (Herceptin).
SO - Endocr Relat Cancer 2002 Jun;9(2):75-85
AD - Breast Unit, The Royal Marsden Hospital and Institute of Cancer Research, Fulham Rd, London SW3 6JJ, UK. email@example.com
HER-2 is a member of the c-erbB family of receptor tyrosine kinases and is overexpressed by 20-30% of human breast cancers. HER-2 overexpression is an independent adverse prognostic factor and may also predict for response to both chemotherapy and endocrine agents. Trastuzumab is a humanised monoclonal antibody that binds with high affinity to the extracellular domain of HER-2. In HER-2-overexpressing preclinical models trastuzumab has been shown to have a marked antiproliferative effect and demonstrates synergy with a number of cytotoxic drugs. Several phase II and phase III clinical trials have now been performed in patients with advanced breast cancer that overexpress HER-2. Trastuzumab was initially shown to be active and well tolerated as a single agent in heavily pretreated women. Subsequently, studies of first-line treatment for metastatic breast cancer have demonstrated an improvement in survival for trastuzumab when used in combination with either paclitaxel or an anthracycline-cyclophosphamide regimen compared with chemotherapy alone. Unexpectedly, the combination of trastuzumab and the anthracycline-containing regimen was associated with a significant incidence of cardiac dysfunction. The benefit of trastuzumab is generally confined to patients whose tumours have gene amplification as detected by fluorescence in situ hybridisation (FISH) and this is tightly associated with immunohistochemical (IHC) staining at the highest (3+) level. A small number of patients have IHC 2+ tumours together with FISH evidence of gene amplification and may also derive benefit from treatment. Trastuzumab has also been shown to be effective when used as first-line monotherapy for advanced breast cancer. Trials to date have employed trastuzumab in a weekly schedule, but there is emerging evidence that a three-weekly regimen may be as effective. Trastuzumab has shown encouraging activity when used with other agents including docetaxel and vinorelbine. The combination of trastuzumab, docetaxel, and platinum salts also appears to be very active. The role of trastuzumab as adjuvant therapy for early breast cancer is being tested in a number of large randomised trials.
UI - 12177098
AU - Osborne CK; Pippen J; Jones SE; Parker LM; Ellis M; Come S; Gertler SZ;
TI - May JT; Burton G; Dimery I; Webster A; Morris C; Elledge R; Buzdar A Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial.
SO - J Clin Oncol 2002 Aug 15;20(16):3386-95
AD - Breast Center at Baylor College of Medicine, 1 Baylor Plaza, MS 600, Houston, TX 77030, USA. firstname.lastname@example.org
PURPOSE: To compare the efficacy and tolerability of fulvestrant (formerly ICI 182,780) with anastrozole in the treatment of advanced breast cancer in patients whose disease progresses on prior endocrine treatment. PATIENTS AND METHODS: In this double-blind, double-dummy, parallel-group study, postmenopausal patients were randomized to receive either an intramuscular injection of fulvestrant 250 mg once monthly or a daily oral dose of anastrozole 1 mg. The primary end point was time to progression (TTP). Secondary end points included objective response (OR) rate, duration of response (DOR), and tolerability. RESULTS: Patients (n = 400) were followed for a median period of 16.8 months. Fulvestrant was as effective as anastrozole in terms of TTP (hazard ratio, 0.92; 95.14% confidence interval [CI], 0.74 to 1.14; P =.43); median TTP was 5.4 months with fulvestrant and 3.4 months with anastrozole. OR rates were 17.5% with both treatments. Clinical benefit rates (complete response + partial response + stable disease > or = 24 weeks) were 42.2% for fulvestrant and 36.1% for anastrozole (95% CI, -4.00% to 16.41%; P =.26). In responding patients, median DOR (from randomization to progression) was 19.0 months for fulvestrant and 10.8 months for anastrozole. Using all patients, DOR was significantly greater for fulvestrant compared with anastrozole; the ratio of average response durations was 1.35 (95% CI, 1.10 to 1.67; P < 0.01). Both treatments were well tolerated. CONCLUSION: Fulvestrant was at least as effective as anastrozole, with efficacy end points slightly favoring fulvestrant. Fulvestrant represents an additional treatment option for postmenopausal women with advanced breast cancer whose disease progresses on tamoxifen therapy.
UI - 12177099
AU - Howell A; Robertson JF; Quaresma Albano J; Aschermannova A; Mauriac L;
TI - Kleeberg UR; Vergote I; Erikstein B; Webster A; Morris C Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment.
SO - J Clin Oncol 2002 Aug 15;20(16):3396-403
AD - Department of Medical Oncology, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, United Kingdom. email@example.com
PURPOSE: To compare the efficacy and tolerability of fulvestrant (formerly ICI 182,780) and anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. PATIENTS AND METHODS: Patients (n = 451) with advanced breast cancer were randomized to receive fulvestrant 250 mg as a once-monthly (one x 5 mL) intramuscular injection or an oral dose of anastrozole 1 mg in this open, parallel-group, multicenter trial. The primary end point was time to progression (TTP). Secondary end points included objective response (OR) rates, defined as complete response (CR) or partial response (PR), duration of response (DOR), and tolerability. RESULTS: Patients were followed for a median period of 14.4 months. In terms of TTP, fulvestrant was as effective as anastrozole (hazard ratio, 0.98; confidence interval [CI], 0.80 to 1.21; P =.84). Median TTP was 5.5 months for fulvestrant and 5.1 months for anastrozole. OR rates showed a numerical advantage for fulvestrant (20.7%) over anastrozole (15.7%) (odds ratio, 1.38; CI, 0.84 to 2.29; P =.20). Clinical benefit rates (CR + PR + stable disease > or = 24 weeks) were 44.6% for fulvestrant and 45.0% for anastrozole. Median DOR was 14.3 months for fulvestrant and 14.0 months for anastrozole. Both treatments were well tolerated, with 3.2% and 1.3% of fulvestrant- and anastrozole-treated patients, respectively, withdrawn from treatment because of an adverse event. CONCLUSION: Fulvestrant was as effective as anastrozole. These data confirm that fulvestrant is an additional, effective, and well-tolerated treatment for advanced breast cancer in postmenopausal women whose disease progressed on prior endocrine therapy.
UI - 11922402
AU - Elkak AE; Mokbel K
TI - Pure antiestrogens and breast cancer.
SO - Curr Med Res Opin 2001;17(4):282-9
AD - The Breast Cancer Centre, St George's Hospital and Medical School, London, UK.
Tamoxifen, which is the most commonly used drug for treatment of breast cancer, has both estrogen agonist and antagonist actions. Pure antiestrogens are devoid of any estrogen agonist effects. ICI 182,780 (fulvestrant) (Faslodex) and ICI 164,384 are competitive inhibitors of estrogen by binding to the estrogen receptor (ER). Preclinical and clinical studies show that fulvestrant and ICI 164,384 are more potent than tamoxifen in inhibiting the growth of breast cancer cells. They are devoid of any estrogen-agonist action on the uterus and vagina but lack the beneficial effects of tamoxifen on the bone and serum lipid profile. Fulvestrant is the first pure antiestrogen to complete phase III clinical trials. Such studies have shown that fulvestrant is at least as good as anastrozole in the treatment of post-menopausal women with advanced breast cancer who had relapsed or progressed on prior endocrine therapy. The drug was well tolerated and only minor side-effects were reported. Its potential role in the adjuvant setting will be determined by its adverse effects on bone mass and serum lipids. EM-800 and EM-652 are the most potent pure antiestrogens and EM-652 has the highest affinity of all antiestrogens to ER. They have no stimulatory effects on the uterus or vagina. It seems reasonable to expect that pure antiestrogens will be good alternatives to tamoxifen and aromatase inhibitors in the treatment of breast cancer.
UI - 12065118
AU - Kitagawa K; Yamakado K; Nakatsuka A; Tanaka N; Matsumura K; Takeda K;
TI - Kawarada Y Preoperative transcatheter arterial infusion chemotherapy for locally advanced breast cancer (stage IIIb) for down-staging and increase of resectability.
SO - Eur J Radiol 2002 Jul;43(1):31-6
AD - Department of Radiology, Mie University School of Medicine, Tsu, Japan. firstname.lastname@example.org
OBJECTIVES: To evaluate the clinical usefulness of preoperative transcatheter arterial infusion chemotherapy (TAIC) for locally advanced breast cancer. METHODS: Seven patients with unresectable locally advanced breast cancer (stage IIIb) underwent TAIC percutaneously 1-3 times (mean, 1.7 times) until tumors became resectable. Anticancer drugs were injected into both the internal mammary and the distal subclavian arteries. RESULTS: There was no major complication related to the procedure. The mean tumor size was significantly decreased from 10.0+/-3.9 to 5.1+/-2.5 cm (P=0.0086). Skin and muscle invasions were improved in two patients (28%) and lymph nodes disappeared in one patient (14%). In two patients (28%), down-staging was achieved from stage IIIb to stage IIIa. All tumors turned into resectable, and mastectomy was performed with a mean period of 35 days (range 9-60 days) after TAIC. Marked decrease in tumor size allowed one patient to receive breast-conserving surgery. There was no local recurrence in any patient. However, five patients (71%) experienced distant metastases. The 3-year disease free and overall survival were 0 and 71.4%, respectively. CONCLUSIONS: TAIC for locally advanced breast cancer is useful in reducing tumor size and achieving down-staging in a relatively short period, leading to an expanded surgical indication.
UI - 12149294
AU - Powles T; Paterson S; Kanis JA; McCloskey E; Ashley S; Tidy A;
TI - Rosenqvist K; Smith I; Ottestad L; Legault S; Pajunen M; Nevantaus A; Mannisto E; Suovuori A; Atula S; Nevalainen J; Pylkkanen L Randomized, placebo-controlled trial of clodronate in patients with primary operable breast cancer.
SO - J Clin Oncol 2002 Aug 1;20(15):3219-24
AD - Royal Marsden National Health Service Trust, Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, UK. email@example.com
PURPOSE: The development of bone metastases depends on tumor-induced osteoclastic resorption of bone, which may be inhibited by the antiosteolytic bisphosphonate clodronate. Given to patients with primary breast cancer, clodronate might reduce the subsequent incidence of bone metastases. PATIENTS AND METHODS: This double-blind, multicenter trial accrued 1,069 assessable patients with operable breast cancer between 1989 and 1995. All patients received surgery, radiotherapy, chemotherapy, and tamoxifen as required. Patients were randomized to receive oral clodronate 1,600 mg/d or a placebo for 2 years starting within 6 months of primary treatment. The primary end point was relapse in bone, analyzed on an intent-to-treat basis, during the medication period and during the total follow-up period (median follow-up, 2,007 days). Secondary end points were relapse in other sites, mortality, and toxicity. RESULTS: During the total follow-up period, there was a nonsignificant reduction in occurrence of bone metastases (clodronate, n = 63; placebo, n = 80; hazards ratio [HR], 0.77; 95% confidence interval [CI], 0.56 to 1.08; P =.127). During the medication period there was a significant reduction in the occurrence of bone metastases (clodronate, n = 12; placebo, n = 28; HR, 0.44; 95% CI, 0.22 to 0.86; P =.016). The occurrence of nonosseous metastases was similar (clodronate, n = 112; placebo, n = 128; P =.257), but there was a significant reduction in mortality (clodronate, n = 98; placebo, n = 129; P =.047) during the total follow-up period. CONCLUSION: Clodronate, given to patients with primary operable breast cancer, may reduce the occurrence of bone metastases, although this reduction was only significant during this medication period. There was a significant reduction in mortality.
UI - 12149306
AU - Winer EP; Hudis C; Burstein HJ; Chlebowski RT; Ingle JN; Edge SB;
TI - Mamounas EP; Gralow J; Goldstein LJ; Pritchard KI; Braun S; Cobleigh MA; Langer AS; Perotti J; Powles TJ; Whelan TJ; Browman GP American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for women with hormone receptor-positive breast cancer: status report 2002.
SO - J Clin Oncol 2002 Aug 1;20(15):3317-27
AD - Health Services Research Department, American Society of Clinical Oncology, 1900 Duke Street, Suite 200, Alexandria, VA 22314, USA. firstname.lastname@example.org
OBJECTIVE: To conduct an evidence-based technology assessment to determine whether the routine use of anastrozole or any of the aromatase inhibitors in the adjuvant breast cancer setting is appropriate for broad-based conventional use in clinical practice. POTENTIAL INTERVENTIONS: Anastrozole, letrozole, and exemestane. OUTCOMES: Outcomes of interest include breast cancer incidence, breast cancer-specific survival, overall survival, and net health benefit. EVIDENCE: A comprehensive, formal literature review was conducted for relevant topics and is detailed in the text. Testimony was collected from invited experts and interested parties. The American Society of Clinical Oncology (ASCO)-prescribed technology assessment procedure was followed. BENEFITS/HARMS: The ASCO panel recognizes that a woman and her physician's decision regarding adjuvant hormonal therapy is complex and will depend on the importance and weight attributed to information regarding both cancer and non-cancer-related risks and benefits. CONCLUSION: The panel was influenced by the compelling, extensive, and long-term data available on tamoxifen. Overall, the panel considers the results of the Arimidex (anastrozole) or Tamoxifen Alone or in Combination (ATAC) trial and the extensive supporting data to be very promising but insufficient to change the standard practice at this time therapy for women with hormone receptor-positive breast cancer. The panel recommends that physicians discuss the available information with patients, and, in making a decision, acknowledge that treatment approaches can change over time. Individual health care providers and their patients will need to come to their own conclusions, with careful consideration of all of the available data. (Specific questions addressed by the panel are summarized in Appendix 3.) VALIDATION: The conclusions of the panel were endorsed by the ASCO Health Services Research Committee and the ASCO Board of Directors.
UI - 12149314
AU - Panasci LC
TI - HER-2/neu serum levels vis-a-vis hormonal response in metastatic breast cancer.
SO - J Clin Oncol 2002 Aug 1;20(15):3357; discussion 3357
UI - 1498061
AU - Mauriac L; Durand M; Chauvergne J; Dilhuydy JM; Bonichon F
TI - Randomized trial of adjuvant chemotherapy for operable breast cancer comparing i.v. CMF to an epirubicin-containing regimen [see comment]
SO - Ann Oncol 1992 Jun;3(6):439-43
AD - Fondation Bergonie, Comprehensive Cancer Center of Southwest of France, Bordeaux. than 3 cm were treated by surgery +/- radiotherapy. All of them had axillary node involvement (N+) and/or lacked estrogen and progesterone steroid receptors (EPR-). They were randomized in an adjuvant chemotherapy trial comparing 9 intravenous CMF courses (cyclophosphamide, methotrexate, 5FU)--113 patients--to a polychemotherapy consisting of 3 courses of MTV (mitomycin C, thiotepa, vindesine) plus 3 courses of EVM (epirubicin, vincristine, methotrexate)--115 patients. Prognostic factors were well balanced between the two treatment groups. With a 59-month median follow-up, local breast relapses are more frequent in the CMF group, but regional and metastatic recurrences are the same in the two groups. Overall survival is identical. Toxicity is different: alopecia and neurotoxicity are more frequent in the MTV+EVM group, but general and digestive toxicities are equivalent. Haematologic toxicity is greater in the CMF group, requiring more frequent dosage reductions.
UI - 8922194
AU - Regazzoni S; Pesce G; Marini G; Cavalli F; Goldhirsch A
TI - Low-dose continuous intravenous infusion of 5-fluorouracil for metastatic breast cancer.
SO - Ann Oncol 1996 Oct;7(8):807-13
AD - Department of Oncology, Ospedale Civico, Lugano, Switzerland.
BACKGROUND: Third-line chemotherapies for advanced breast cancer are difficult to tailor to the individual patient because of reduced tolerance and significant toxicity. Treatment with a continuous intravenous infusion of low-dose 5-fluorouracil (FU-LDCI) is generally well tolerated and thus, a reasonable option for heavily pretreated patients. PATIENTS AND METHODS: From 1989 to 1995, 106 consecutive patients with advanced breast cancer were treated with FU-LDCI. 5-Fluorouracil was given at an initial daily dose of 250 mg/m2 administered continuously with the aid of an elastomer, non-electronic pump through a permanent central venous line for 21 days followed by a 7-day rest. The median age was 56 years (range, 30-82), the median ECOG Performance Status was 1 (range 0-4) and the median number of metastatic sites was 2 (range 1-4). Sixty-one percent of the patients had previously received more than 2 chemotherapy regimens which in 81% included adriamycin, and in 90% 5-fluorouracil. RESULTS: Eighty patients were evaluable for objective response: 17 of them had partial responses (21%, 95% CI: 14%-31%) and 23 stable disease (29%, 95% CI: 20%-40%). One-hundred five patients were evaluable for subjective response, with 46 reporting improvement (44%, 95% CI: 35%-54%). Previous treatments with either 5-fluorouracil or adriamycin did not predict response to FU-LDCI. Median time to progression for patients with a partial response or stable disease was 259 days (range 82-737). The overall survival for the populations as a whole was 274 days (range 13-2264), and the median dose received was 1904 mg/week (range 753-4329). The main toxic effects were grades I and II mucositis, and nausea and vomiting (observed in 31% and 28%, respectively). Grade III toxicities were uncommon: mucositis in 3%, nausea and vomiting in 3%, anemia, thrombocytopenia and hepatitis in 2%, and skin toxicity (hand-foot syndrome) in 1%. Catheter-related thrombosis was observed in 2% of the patients, and there were no pump failures. A questionnaire concerning the impact of the treatment upon quality of life was completed by all of the 13 patients who were alive at the time of evaluation of the results, and all of them rated FU-LDCI as easy to tolerate. The monthly cost of FU-LDCI (US$1,051.00 in Switzerland) was lower than the cost of weekly low-dose adriamycin (US$1,483.00 in Switzerland), a treatment which is often used as a palliative regimen in similar circumstances. CONCLUSION: FU-LDCI is a useful, cost-effective third-line treatment for patients with metastatic breast cancer who need palliation with cytotoxic drugs.
UI - 11683751
AU - Grogan M; Tabar L; Chua B; Chen HH; Boyages J
TI - Estimating the benefits of adjuvant systemic therapy for women with early breast cancer.
SO - Br J Surg 2001 Nov;88(11):1513-8
AD - New South Wales Breast Cancer Institute, Westmead Hospital, University of Sydney, Westmead, New South Wales, Australia.
BACKGROUND: Prognostic factors are commonly used to help identify women with node-negative breast cancer at high risk of recurrence. Although many are available, knowing which risk factor or combination of factors to use to estimate prognosis for an individual woman is often difficult. This study documented the baseline prognoses for a group of women with node-negative breast cancers, and estimated the potential benefits of adjuvant systemic therapy. METHODS: Ten-year, actuarial, cause-specific survival based on tumour size and histological grade using data from the Swedish Two-County Trial of mammographic screening was calculated for 1200 women with node-negative cancers of less than 30 mm diameter. The benefits of adjuvant systemic therapy for these women were then estimated using the published odds reductions in death from adjuvant systemic therapy from the Early Breast Cancer Trialists' Collaborative Group overview. RESULTS: The absolute 10-year survival benefits for subgroups of women based on tumour size and histological grade were estimated for women aged under 50 years by the addition of chemotherapy, and over 50 years by the addition of tamoxifen and/or chemotherapy. CONCLUSION: Decisions about adjuvant systemic therapy in women with node-negative breast cancer need to be individualized, taking into account treatment efficacy and toxicity. The quantitative methods presented in this paper facilitate such decisions.
UI - 12091062
AU - Costa SD; Lange S; Klinga K; Merkle E; Kaufmann M
TI - Factors influencing the prognostic role of oestrogen and progesterone receptor levels in breast cancer--results of the analysis of 670 patients with 11 years of follow-up.
SO - Eur J Cancer 2002 Jul;38(10):1329-34
AD - Department of Obstetrics and Gynecology, University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. email@example.com
In the last two decades, the prognostic role of the steroid hormone receptors has been the subject of a myriad of publications. Nevertheless, its relevance after long-term follow-up is still not clear. The confusion about the prognostic value is mainly due to the difficulty in comparing analyses. Despite different study-designs and statistical approaches, oestrogen (ER) and progesterone (PR) receptors are widely accepted as prognostic factors. Data from 670 breast cancer patients with a median follow-up of 11.4 years were analysed retrospectively. ER and PR were measured by the dextran-coated charcoal (DCC) assay. To investigate the time dependence of the prognostic relevance of ER and PR, separate analyses were done for follow-up shorter and longer than 5 years. Special focus was directed at patients < or =50 and >50 years, node-negative women, in particular those without adjuvant therapy. Univariate and multivariate analyses were performed. In univariate analysis, ER and PR were associated with a significantly longer overall survival at the cut-off levels 10, 20 or 100 fmol/mg protein. The significant survival benefit occurred in the first 5 years of follow-up and remained unchanged in the following period. In the multivariate analyses, only the PR was of significant prognostic value (for PR> or =20 fmol/mg P=0.036, for PR> or =100 P=0.01, Cox analysis). In patients younger than 51 years, only PR was an independent prognosticator at the cut-off level of 100 fmol/mg protein, while in patients >50 years both hormone receptors were not significant. In N0 patients, only the PR reached long-term prognostic independence at a cut-off point of > or =100 fmol/mg (P=0.018). In addition, in the group of node-negative women < or =50 years without adjuvant therapy the PR level reached prognostic significance. The hormone receptor status was a prognostic factor only during the first 5 years of follow-up. Our data suggest that age, lymph node status, length of follow-up and probably the ER/PR assay are important for the evaluation of ER and PR as prognostic variables. In most analyses, PR appeared to be superior to ER in predicting the prognosis of primary breast cancer patients.
UI - 12177795
AU - Somlo G; Simpson JF; Frankel P; Chow W; Leong L; Margolin K; Morgan R
TI - Jr; Raschko J; Shibata S; Forman S; Kogut N; McNamara M; Molina A; Somlo E; Doroshow JH Predictors of long-term outcome following high-dose chemotherapy in high-risk primary breast cancer.
SO - Br J Cancer 2002 Jul 29;87(3):281-8
AD - Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, 1500 E Duarte Road, Duarte, California, CA 91010-3000, USA. firstname.lastname@example.org
We report on a predictive model of long-term outcome in 114 high-risk breast cancer patients treated with high-dose chemotherapy between 1989 and 1994. Paraffin-blocks from 90 of the 114 primaries were assessed for the presence of five risk factors: grade, mitotic index, protein expression of p53, HER2/neu, and oestrogen/progesterone receptor status; we could analyse the effect of risk factors in 84 of these 90 tumours. Seven-year relapse-free and overall survival was 58% (95% confidence interval 44-74%) and 82% (95% confidence interval 71-94%) vs 33% (95% confidence interval 21-52%) and 41% (95% confidence interval 28-60%) for patients whose primary tumours displayed > or =3 risk factors vs patients with < or =2 risk factors. For the entire group of 168 high-risk breast cancer patients, inflammatory stage IIIB disease and involved post-mastectomy margins were associated with decreased relapse-free survival and overall survival; patients treated with non-doxorubicin containing standard adjuvant therapy experienced worse overall survival (RR, 2.08; 95% confidence interval 1.04 to 4.16; P=0.04), while adjuvant tamoxifen improved overall survival (RR, 0.65; 95% confidence interval 0.41-1.01; P=0.054). Future trial designs and patient selection for studies specific for high-risk breast cancer patients should include appropriate prognostic models. Validation of such models could come from recently completed randomised, prospective trials. Copyright 2002 Cancer Research UK
UI - 12177804
AU - Anderson TJ; Dixon JM; Stuart M; Sahmoud T; Miller WR
TI - Effect of neoadjuvant treatment with anastrozole on tumour histology in postmenopausal women with large operable breast cancer.
SO - Br J Cancer 2002 Jul 29;87(3):334-8
AD - Department of Pathology, Western General Hospital, Edinburgh EH4 2XU, UK.
Anastrozole is an orally active, non-steroidal aromatase inhibitor which appears effective as neoadjuvant treatment of breast cancer. Histological changes have been evaluated in biopsies from large, oestrogen-receptor rich, operable breast tumours in postmenopausal women following 12 weeks of neoadjuvant anastrozole treatment (1 mg (n=12) or 10 mg (n=11)). Of the 23 patients, 18 had a clinical response following treatment. Compared with pre-treatment biopsies anastrozole-treated specimens displayed decreased cellularity and/or increased fibrosis in 15 tumours; changes in gland formation, nuclear pleomorphism, or mitoses, in 12 cases; and a reduction in Mib1 score in all tumours. Marked changes in apoptotic scores were seen following treatment but the direction of effect was inconsistent. In all 17 tumours which were positive for progesterone receptors before therapy, treatment was associated with reduced staining for progesterone receptors. There was no consistent effect of treatment on oestrogen-receptor expression. It is concluded that neoadjuvant anastrozole treatment in this patient group has marked effects on tumour histopathology but these do not always correlate with clinical response. Copyright 2002 Cancer Research UK
UI - 12195747
AU - Andersson J; Linderholm B; Greim G; Lindh B; Lindman H; Tennvall J;
TI - Tennvall-Nittby L; Pettersson-Skold D; Sverrisdottir A; Soderberg M; Klaar S; Bergh J A population-based study on the first forty-eight breast cancer patients receiving trastuzumab (Herceptin) on a named patient basis in Sweden.
SO - Acta Oncol 2002;41(3):276-81
AD - Department of Oncology, Radiumhemmet, Karolinska Institute and Hospital, SE-171 76 Stockholm, Sweden. email@example.com
Several studies have presented data on the efficacy and tolerability of trastuzumab within clinical trials. As a minority of patients is included in these trials, we undertook this retrospective study to describe trastuzumab therapy in clinical routine and its tolerability. We reviewed the medical records of the first 48 patients in Sweden who received treatment with trastuzumab on a named patient basis with (n = 29) and without (n = 19) chemotherapy. Forty-six patients had metastatic disease and had failed to respond to several prior regimens before starting antibody treatment. Two patients had locally advanced breast cancer failing on given neoadjuvant therapy. Patients with breast cancers with strong (3+) c-erbB-2 overexpression tended to have an improved survival from start of trastuzumab treatment versus those with a moderate (2+) overexpression (p = 0.09). Adverse events were registered in 22 patients (46%). The most common and acute side effects were fever and chills (7 patients, 15%). The toxicity seemed reasonable but two patients (4%) suffered serious cardiac events, both of them having received previous treatment with antracyclines.
UI - 7848882
AU - Valagussa P; Moliterni A; Terenziani M; Zambetti M; Bonadonna G
TI - Second malignancies following CMF-based adjuvant chemotherapy in resectable breast cancer.
SO - Ann Oncol 1994 Nov;5(9):803-8
AD - Division of Medical Oncology, Istituto Nazionale Tumori, Milan, Italy.
BACKGROUND: Only a few studies have evaluated the long-term effects of adjuvant chemotherapy for breast cancer. Furthermore, neither the relation between the risk of second malignancies and type of adjuvant regimen utilized nor the interaction between chemotherapy and breast irradiation or age of the patients have been described in detail. METHODS: A total of 2,465 patients entered into prospective studies of CMF-based adjuvant chemotherapy carried out at the Milan Cancer follow-up was 12.0 years and detailed information about therapy was available for all patients. RESULTS: At 15 years, the cumulative actuarial risk of second malignancies (excluding contralateral breast cancer and basal skin cancer) was 6.7% +/- 0.8% for the total series. The figures were 8.4% +/- 2.9% after local-regional treatment alone, 6.4% +/- 0.9% following CMF, and 5.1% +/- 1.0% following CMF plus Adriamycin (doxorubicin; Farmitalia-Carlo Erba, Milan, Italy). Compared to the general female population, the relative risk following CMF-based adjuvant chemotherapy was 1.29. Three patients, all of whom had received CMF-based chemotherapy, developed acute non-lymphocytic leukemia (cumulative risk 0.23% +/- 0.15%; relative risk 2.3). No differences were evident when breast irradiation was considered, but the cumulative risk of second tumors was slightly higher in women aged > or = 50 years at surgery (7.7% +/- 1.3%) than in younger patients (6.0% +/- 1.0%). CONCLUSIONS: At present, there is no evidence of a significantly increased risk of second malignancies following adjuvant CMF-based chemotherapy such as the one given in this case series. A low risk of acute leukemia was associated with the cumulative total dose of cyclophosphamide administered, and breast irradiation did not enhance this risk. IMPLICATIONS: Our findings suggest that there is no reason to omit alkylating agents from short-term effective adjuvant chemotherapy.
UI - 12187169
AU - Warren JL; Harlan LC; Fahey A; Virnig BA; Freeman JL; Klabunde CN;
TI - Cooper GS; Knopf KB Utility of the SEER-Medicare data to identify chemotherapy use.
SO - Med Care 2002 Aug;40(8 Suppl):IV-55-61
AD - Applied Research Program, National Cancer Institute, Bethesda, Maryland 20892-7344, USA.firstname.lastname@example.org
BACKGROUND: Medicare claims include codes for chemotherapy administration and specific drugs given, and researchers are increasingly using these data to measure the use of chemotherapy. However, the validity and completeness of these data as a source of information has not been established. OBJECTIVES: This analysis is intended to assess the utility of the Medicare claims to capture chemotherapy use. METHODS: Persons with breast, colorectal, and ovarian cancer were identified from the linked SEER-Medicare data. Their Medicare claims were reviewed to determine if there were any bills for chemotherapy, and if so, if there were claims for specific agents. This information was compared with data on the first course of treatment obtained from hospitals and treating physicians by the SEER registries through an NCI-supported Patterns of Care Studies (POC). Agreement was measured using kappa statistics. The sensitivity of the Medicare claims to capture chemotherapy, as reported from the POC data, was also measured. An additional comparison assessed the agreement between the two data sources concerning which specific drugs had been given. RESULTS: For all of the cancers, there was a high level of agreement between the Medicare claims and the POC data regarding whether or not the patient had received chemotherapy (kappa >or=0.73). The sensitivity of the Medicare data to determine if a person had received chemotherapy was high (>or=88%). In cases where the Medicare claim included a code for a specific drug, there high agreement between Medicare and POC about the specific drug given in breast and colorectal cancers, although the agreement was lower for ovarian cancers. The sensitivity of the Medicare claims to identify specific agents varies by cancer type. CONCLUSIONS: The Medicare claims can be used to identify which persons are receiving chemotherapy. The utility of Medicare data to measure treatment with specific agents varies by cancer type and specific agent. For some cancers, it is possible to use these claims to assess use of specific drugs, while for other drugs the data are limited. <