Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors

BACKGROUND: In 1982, the National Surgical Adjuvant Breast and Bowel Project initiated a randomized, double-blinded, placebo-controlled trial (B-14) to determine the effectiveness of adjuvant tamoxifen therapy in patients with primary operable breast cancer who had estrogen receptor-positive tumors and no axillary lymph node involvement. The findings indicated that tamoxifen therapy provided substantial benefit to patients with early stage disease. However, questions arose about how long the observed benefit would persist, about the duration of therapy necessary to maintain maximum benefit, and about the nature and severity of adverse effects from prolonged treatment. PURPOSE: We evaluated the outcome of patients in the B-14 trial through 10 years of follow-up. In addition, the effects of 5 years versus more than 5 years of tamoxifen therapy were compared. METHODS: In the trial, patients were initially assigned to receive either tamoxifen at 20 mg/day (n = 1404) or placebo (n = 1414). Tamoxifen-treated patients who remained disease free after 5 years of therapy were then reassigned to receive either another 5 years of tamoxifen (n = 322) or 5 years of placebo (n = 321). After the study began, another group of patients who met the same protocol eligibility requirements as the randomly assigned patients were registered to receive tamoxifen (n = 1211). Registered patients who were disease free after 5 years of treatment were also randomly assigned to another 5 years of tamoxifen (n = 261) or to 5 years of placebo (n = 249). To compare 5 years with more than 5 years of tamoxifen therapy, data relating to all patients reassigned to an additional 5 years of the drug were combined. Patients who were not reassigned to either tamoxifen or placebo continued to be followed in the study. Survival, disease-free survival, and distant disease-free survival (relating to failure at distant sites) were estimated by use of the Kaplan-Meier method; differences between the treatment groups were assessed by use of the logrank test. The relative risks of failure (with 95% confidence intervals [CIs]) were determined by use of the Cox proportional hazards model. Reported P values are two-sided. RESULTS: Through 10 years of follow-up, a significant advantage in disease-free survival (69% versus 57%, P < .0001; relative risk = 0.66; 95% CI = 0.58-0.74), distant disease-free survival (76% versus 67%, P < .0001; relative risk = 0.70; 95% CI = 0.61-0.81), and survival (80% versus 76%, P = .02; relative risk = 0.84; 95% CI = 0.71-0.99) was found for patients in the group first assigned to receive tamoxifen. The survival benefit extended to those 49 years of age or younger and to those 50 years of age or older. Tamoxifen therapy was associated with a 37% reduction in the incidence of contralateral (opposite) breast cancer (P = .007). Through 4 years after the reassignment of tamoxifen-treated patients to either continued-therapy or placebo groups, advantages in disease-free survival (92% versus 86%, P = .003) and distant disease-free survival (96% versus 90%, P = .01) were found for those who discontinued tamoxifen treatment. Survival was 96% for those who discontinued tamoxifen compared with 94% for those who continued tamoxifen treatment (P = .08). A higher incidence of thromboembolic events was seen in tamoxifen-treated patients (through 5 years, 1.7% versus 0.4%). Except for endometrial cancer, the incidence of second cancers was not increased with tamoxifen therapy. CONCLUSIONS AND IMPLICATIONS: The benefit from 5 years of tamoxifen therapy persists through 10 years of follow-up. No additional advantage is obtained from continuing tamoxifen therapy for more than 5 years.     

A residue number system implementation of real orthogonaltransforms

Previous work has focused on performing residue computations that are quantized within a dense ring of integers in the real domain. The aims of this paper are to provide an efficient algorithm for the approximation of real input signals, with arbitrarily small error, as elements of a quadratic number ring and to prove residual number system moduli restrictions for simplified multiplication within the ring. The new approximation scheme can be used for implementation of real-valued transforms and their multidimensional generalizations     

Wrapping Effect and Wrapping Function

We study the wrapping effect associated with validated interval methods for numerical solution of the initial value problem for ordinary differential equations by introducing a new concept of wrapping function. The wrapping function is proved to be the limit of the enclosures of the solution produced by methods of certain type. There is no wrapping effect if and only if the wrapping function equals the optimal interval enclosure of the solution.     

Lumpectomy and radiation therapy for the treatment of intraductal breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-17

PURPOSE: In 1993, findings from a National Surgical Adjuvant Breast and Bowel Project (NSABP) trial to evaluate the worth of radiation therapy after lumpectomy concluded that the combination was more beneficial than lumpectomy alone for localized intraductal carcinoma-in-situ (DCIS). This report extends those findings. PATIENTS AND METHODS: Women (N = 818) with localized DCIS were randomly assigned to lumpectomy or lumpectomy plus radiation (50 Gy). Tissue was removed so that resected specimen margins were histologically tumor-free. Mean follow-up time was 90 months (range, 67 to 130). Size and method of tumor detection were determined by central clinical, mammographic, and pathologic assessment. Life-table estimates of event-free survival and survival, average annual rates of occurrence for specific events, relative risks for event-specific end points, and cumulative probability of specific events comprising event-free survival are presented. RESULTS: The benefit of lumpectomy plus radiation was virtually unchanged between 5 and 8 years of follow-up and was due to a reduction in invasive and noninvasive ipsilateral breast tumors (IBTs). Incidence of locoregional and distant events remained similar in both treatment groups; deaths were only infrequently related to breast cancer. Incidence of noninvasive IBT was reduced from 13.4% to 8.2% (P = .007), and of invasive IBT, from 13.4% to 3.9% (P < .0001). All cohorts benefited from radiation regardless of clinical or mammographic tumor characteristics. CONCLUSION: Through 8 years of follow-up, our findings continue to indicate that lumpectomy plus radiation is more beneficial than lumpectomy alone for women with localized, mammographically detected DCIS. When evaluated according to the mammographic characteristics of their DCIS, all groups benefited from radiation.     

Cobalt Recovery from Sulfate Media Applying a Liquid Membrane Containing Cyanex 302

Cobalt recovery from sulfate solutions was studied by using a liquid membrane containing Cyanex 302. The influence of the pH and the concentrations of cobalt and the extractant on the metal equilibrium distribution was established. Kinetic investigations of the cobalt transfer across a liquid membrane containing Cyanex 302 were performed in a rotating film contactor. Sulfuric acid was used as a stripping agent. The results obtained show that cobalt can be successfully recovered from neutral and weakly acidic sulfate solutions. A mathematical model describing the transport of cobalt ions across the liquid membrane was proposed. The local mass transfer coefficients of cobalt ions in the aqueous phases and cobalt‐carrier complex in the organic phase were evaluated on the basis of the experimental data obtained at various conditions as well as on the proposed model.     

The induction of lipid peroxidation in the serum of patients with acute peritonitis

Wound-healing activity of 2% betamicil ointment in comparison with the traditional stimulants of corneal repair regeneration (methyluracyl and solcoseril) was studied in experiments. The rate of epithelialization of a standard trephination wound in rabbit cornea (28 animals), mitotic activity of the anterior corneal epithelium, and strength of the regenerated tissue were assessed after use of different stimulants and in control. A maximal positive effect of local betamicil (2% ointment) was observed: the wounds epithelialized 57% sooner than in control, but there was no reliable difference from solcoseril; the regenerate of linear corneal wound was 1.5 times stronger. Use of this ointment in ophthalmology is validated.