Systemic treatments for women with breast cancer: outcome with relation to screening for the disease

Early detection and proper care of breast cancer are currently the best available approaches to the treatment of patients with the disease. In countries with a breast cancer screening programme, there has been a demonstrated reduction in breast cancer-related mortality. Such reduction has also been observed in Switzerland, a country in which no national programme of screening is available. Although there is no doubt that early diagnosis might have had a major role in reducing breast cancer mortality the magnitude of this effect is unknown. Research with tailored approaches on alternative imaging for early detection of breast cancer in high-risk women and on treatments offered according to proper criteria of responsiveness to therapies is warrante

New treatments for breast cancer: Breakthroughs for patient care or just steps in the right direction?

Three areas of clinical research in breast cancer treatment led to news breaking presentations at the American Society of Clinical Oncology (ASCO) meeting, 1998, in Los Angeles. All three subjects represent important advances in cancer medicine. Prevention: Two related drugs, tamoxifen and raloxifene, were found in placebo controlled trials to significantly reduce the incidence of breast cancer for women at increased risk of developing the disease. Patterns of relapse showed that the reduced rate of breast cancer was exclusively observed for tumors expressing estrogen receptors, while the rate of tumors classified as estrogen-receptor negative was similar for the treatment and the control groups. This may indicate that the observed reduction in breast cancer incidence is due to a treatment effect on occult disease rather than its prevention. We certainly have no adequate information on mortality prevention. Adjuvant therapies: Taxol given every three weeks for four courses following an adjuvant treatment with four courses of doxorubicin and cyclophosphamide (AC) combination was found to be superior to not adding treatment after the four courses of AC in a trial involving 3170 patients. At 22 months of median follow-up, the quoted P-values were P = 0.0077 for disease-free survival and P = 0.039 for overall survival, but these did not cross the prospectively defined interim analysis boundaries for statistical significance at the 0.05 level. The difference was observed early during follow-up, and was exclusively seen in the 40% of patients who had ER-negative primaries and, therefore, did not receive tamoxifen following chemotherapy. One may thus argue that the early difference observed was primarily due to differences in the duration of the treatment regimens in the two groups and the early entry into the trial of patients with particularly aggressive neoplasia (e.g., ER-negative primaries) who would have benefited from a longer duration treatment. Treatment of advanced disease: The use of monoclonal antibodies to c-erb-B2 was found to induce responses in metastatic breast cancer. Patients with tumors expressing c-erb-B2 responded to weekly infusions of this biological agent. It was particularly impressive that the response rate for patients receiving infusion of the monoclonal antibodies together with the cytotoxics was superior to that with chemotherapy alone in a randomized trial. It is important to note that only patients with tumors overexpressing c-erbB-2 (the overall incidence is about 20%) were tested. It must still be demonstrated that the effect of these monoclonal antibodies is indeed confined to cells overexpressing c-erbB-2. Treatment related cardiac tox-icity remains a problem, and the effects of treatment in various subsets of patients need to be defined before starting investigations in the adjuvant setting, which is a clear further objective of this specific research. The significant findings from clinical research opened several new questions, which must be answered before allowing them to be employed in routine patient car

Temperature And Lifetime Measurements In The SSX Wind Tunnel

We describe ion and electron temperature measurements in the Swarthmore Spheromak Experiment (SSX) MHD wind tunnel with the goal of understanding limitations on the lifetime of our Taylor-state plasma. A simple model based on the equilibrium eigenvalue and Spitzer resistivity predicted the lifetime satisfactorily during the first phase of the plasma evolution. We measured an average Tₑ along a chord by taking the ratio of the CIII97.7 nm to CIV155 nm line intensities using a vacuum ultraviolet (VUV) monochromator. We also recorded local measurements of Tₑ and nₑ using a double Langmuir probe in order to inform our interpretation of the VUV data. Our results indicated that the plasma decayed inductively during a large part of the evolution. Ion Doppler spectroscopy measurements suggested that ions cooled more slowly than would be expected from thermal equilibration with the electrons, which maintained a constant temperature throughout the lifetime of the plasma

Systemic treatments for women with breast cancer: outcome with relation to screening for the disease

Early detection and proper care of breast cancer are currently the best available approaches to the treatment of patients with the disease. In countries with a breast cancer screening programme, there has been a demonstrated reduction in breast cancer-related mortality. Such reduction has also been observed in Switzerland, a country in which no national programme of screening is available. Although there is no doubt that early diagnosis might have had a major role in reducing breast cancer mortality the magnitude of this effect is unknown. Research with tailored approaches on alternative imaging for early detection of breast cancer in high-risk women and on treatments offered according to proper criteria of responsiveness to therapies is warranted

Subpopulation Treatment Effect Pattern Plot (STEPP) Methods with R and Stata

We introduce the stepp packages for R and Stata that implement the subpopulation treatment effect pattern plot (STEPP) method. STEPP is a nonparametric graphical tool aimed at examining possible heterogeneous treatment effects in subpopulations defined on a continuous covariate or composite score. More pecifically, STEPP considers overlapping subpopulations defined with respect to a continuous covariate (or risk index) and it estimates a treatment effect for each subpopulation. It also produces confidence regions and tests for treatment effect heterogeneity among the subpopulations. The original method has been extended in different directions such as different survival contexts, outcome types, or more efficient procedures for identifying the overlapping subpopulations. In this paper, we also introduce a novel method to determine the number of subjects within the subpopulations by minimizing the variability of the sizes of the subpopulations generated by a specific parameter combination. We illustrate the packages using both synthetic data and publicly available data sets. The most intensive computations in R are implemented in Fortran, while the Stata version exploits the powerful Mata language

Premenopausal endocrine-responsive early breast cancer: who receives chemotherapy?

Background: The role of chemotherapy in addition to combined endocrine therapy for premenopausal women with endocrine-responsive early breast cancer remains an open question, yet trials designed to answer it have repeatedly failed to adequately accrue. The International Breast Cancer Study Group initiated two concurrent trials in this population: in Premenopausal Endocrine Responsive Chemotherapy (PERCHE), chemotherapy use is determined by randomization and in Tamoxifen and Exemestane Trial (TEXT) by physician choice. PERCHE closed with inadequate accrual; TEXT accrued rapidly. Methods: From 2003 to 2006, 1317 patients (890 with baseline data) were randomly assigned to receive ovarian function suppression (OFS) plus tamoxifen or OFS plus exemestane for 5 years in TEXT. We explore patient-related factors according to whether or not chemotherapy was given using descriptive statistics and classification and regression trees. Results: Adjuvant chemotherapy was chosen for 64% of patients. Lymph node status was the predominant determinant of chemotherapy use (88% of node positive treated versus 46% of node negative). Geography, patient age, tumor size and grade were also determinants, but degree of receptor positivity and human epidermal growth factor receptor 2 status were not. Conclusions: The perceived estimation of increased risk of relapse is the primary determinant for using chemotherapy despite uncertainties regarding the degree of benefit it offers when added to combined endocrine therapy in this populatio

Long-term results of International Breast Cancer Study Group Trial VIII: adjuvant chemotherapy plus goserelin compared with either therapy alone for premenopausal patients with node-negative breast cancer

Background: The International Breast Cancer Study Group Trial VIII compared long-term efficacy of endocrine therapy (goserelin), chemotherapy [cyclophosphamide, methotrexate and fluorouracil (CMF)], and chemoendocrine therapy (CMF followed by goserelin) for pre/perimenopausal women with lymph-node-negative breast cancer. Patients and methods: From 1990 to 1999, 1063 patients were randomized to receive (i) goserelin for 24 months (n = 346), (ii) six courses of ‘classical' CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy (n = 360), or (iii) six courses of CMF plus 18 months goserelin (CMF→ goserelin; n = 357). Tumors were classified as estrogen receptor (ER) negative (19%), ER positive (80%), or ER unknown (1%); 19% of patients were younger than 40. Median follow-up was 12.1 years. Results: For the ER-positive cohort, sequential therapy provided a statistically significant benefit in disease-free survival (DFS) (12-year DFS = 77%) compared with CMF alone (69%) and goserelin alone (68%) (P = 0.04 for each comparison), due largely to the effect in younger patients. Patients with ER-negative tumors whose treatment included CMF had similar DFS (12-year DFS CMF = 67%; 12-year DFS CMF→ goserelin = 69%) compared with goserelin alone (12-year DFS = 61%, P= NS). Conclusions: For pre/perimenopausal women with lymph-node-negative ER-positive breast cancer, CMF followed by goserelin improved DFS in comparison with either modality alone. The improvement was the most pronounced in those aged below 40, suggesting an endocrine effect of prolonged CMF-induced amenorrhe

Predictors of early relapse in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1-98 trial

Background: Aromatase inhibitors are considered standard adjuvant endocrine treatment of postmenopausal women with hormone receptor-positive breast cancer, but it remains uncertain whether aromatase inhibitors should be given upfront or sequentially with tamoxifen. Awaiting results from ongoing randomized trials, we examined prognostic factors of an early relapse among patients in the BIG 1-98 trial to aid in treatment choices. Patients and methods: Analyses included all 7707 eligible patients treated on BIG 1-98. The median follow-up was 2 years, and the primary end point was breast cancer relapse. Cox proportional hazards regression was used to identify prognostic factors. Results: Two hundred and eighty-five patients (3.7%) had an early relapse (3.1% on letrozole, 4.4% on tamoxifen). Predictive factors for early relapse were node positivity (P < 0.001), absence of both receptors being positive (P < 0.001), high tumor grade (P < 0.001), HER-2 overexpression/amplification (P < 0.001), large tumor size (P = 0.001), treatment with tamoxifen (P = 0.002), and vascular invasion (P = 0.02). There were no significant interactions between treatment and the covariates, though letrozole appeared to provide a greater than average reduction in the risk of early relapse in patients with many involved lymph nodes, large tumors, and vascular invasion present. Conclusion: Upfront letrozole resulted in significantly fewer early relapses than tamoxifen, even after adjusting for significant prognostic factor