Purpose: This study was performed to determine the long-term outcome for women with mammographically detected ductal carcinoma
in situ (DCIS; intraductal carcinoma) of the breast treated with ...breast-conserving surgery followed by definitive breast irradiation.
Methods and Materials: An analysis was performed of 422 mammographically detected intraductal breast carcinomas in 418 women from 11 institutions in North America and Europe. All patients were treated with breast-conserving surgery followed by definitive breast irradiation. The median follow-up time was 9.4 years (mean, 9.4 years; range, 0.1–19.8 years).
Results: The 15-year overall survival rate was 92%, and the 15-year cause-specific survival rate was 98%. The 15-year rate of freedom from distant metastases was 94%. There were 48 local failures in the treated breast, and the 15-year rate of any local failure was 16%. The median time to local failure was 5.0 years (mean, 5.7 years; range, 1.0–15.2 years). Patient age at the time of treatment and final pathology margin status from the primary tumor excision were both significantly associated with local failure. The 10-year rate of local failure was 31% for patient age ≤ 39 years, 13% for age 40–49 years, 8% for age 50–59 years, and 6% for age ≥ 60 years (
p = 0.0001). The 10-year rate of local failure was 24% when the margins of resection were positive, 9% when the margins of resection were negative, 7% when the margins of resection were close, and 12% when the margins of resection were unknown (
p = 0.030). Patient age ≤ 39 years and positive margins of resection were both independently associated with an increased risk of local failure (
p = 0.0006 and
p = 0.023, respectively) in the multivariable Cox regression model.
Conclusions: The 15-year results from the present study demonstrated high rates of overall survival, cause-specific survival, and freedom from distant metastases following the treatment of mammographically detected ductal carcinoma
in situ of the breast using breast-conserving surgery and definitive breast irradiation. Younger age and positive margins of resection were both independently associated with an increased risk of local failure. The 15-year results in the present study serve as an important benchmark for comparison with other treatment modalities. These results support the use of breast-conserving surgery and definitive breast irradiation for the treatment of appropriately selected patients with mammographically detected ductal carcinoma
in situ of the breast.
Two trials were conducted to evaluate effects of feeding supplemental fibrolytic enzymes or soluble sugars and malic acid on milk production. In trial 1, 257 cows at four sites were fed a basal diet ...consisting of no more than 60% of forage DM as corn silage and less than 40% as alfalfa hay. Cows were assigned randomly within site, parity, and two stages of lactation to: 1) control; 2) enzyme A; 3) enzyme B; and 4) soluble sugars and malic acid. There was a 14-d pretreatment and an 84-d treatment period. Enzyme solutions were sprayed on either the forage component or the TMR each day while mixing feed. Trial 2 was similar, except 122 cows at one site in the United Kingdom were fed diets containing forage that was 75% corn silage and 25% grass silage, and all cows began the study between 25 to 31 DIM. Mean milk productions for 233 cows that completed trial 1 were 32.9, 32.5, 32.4, and 32.9kg/d for control, enzyme A, enzyme B, and soluble sugars and malic acid, respectively. Mean milk productions for 116 cows that completed trial 2 were 28.2, 27.9, 28.8, and 28.4kg/d, respectively. In vitro analyses of the activities of enzyme solutions indicated that all major cellulose and hemicellulose degrading activities were present; however, the pH optima (approximate pH = 4 to 5) were more acidic, and the temperature optimum (approximately 50°C) was greater than normal pH and temperature in the rumen. If fibrolytic activity in the rumen is a major mechanism of action of supplemental fibrolytic enzymes, it appears that considerable activity of these preparations was lost due to conditions in the rumen. In conclusion, feeding supplemental fibrolytic enzymes or malic acid with soluble sugars had no effect on milk production under the conditions used in this study.
A dry period, typically 40 to 60 d, between lactations is believed to be required to maximize milk yield in the subsequent lactation. Several hypotheses have been proposed to explain the requirement ...for the dry period, including (1) replenishment of body reserves, (2) regeneration of mammary tissue, and (3) optimization of benefits from endocrine events near the time of parturition. Continuously milked cows or glands have depressed milk yields but no differences in mammary DNA content or cell number. Nutritional status and endocrine hormones are not factors in reduced milk yield in continuously milked glands. Data from continuous lactation studies suggest that depressed milk yields are due to reduced functionality of mammary parenchyma. There is a need to reevaluate effects of continuous lactation on milk yield in today's high-producing dairy cow because studies on this topic were done using cows achieving peak milk production of 18 to 30kg/d compared with 45 to 50kg/d in today's dairy cows. Another factor that has not been considered in conjunction with current milk production levels is the use of bovine somatotropin (bST). Supplementation with bST increases milk yield, improves lactation persistency, and may improve milk yield in continuously milked cows. Future research goals are to examine the effects of continuous lactation in high-producing cows and to determine the effects of bST on milk yield and mammary functionality in continuously milked cows.
Animal feeding studies were conducted with rats, broiler chickens, catfish and dairy cows as part of a safety assessment program for a soybean variety genetically modified to tolerate in-season ...application of glyphosate. These studies were designed to compare the feeding value (wholesomeness) of two lines of glyphosate-tolerant soybeans (GTS) to the feeding value of the parental cultivar from which they were derived. Processed GTS meal was incorporated into the diets at the same concentrations as used commercially; dairy cows were fed 10 g/100 g cracked soybeans in the diet, a level that is on the high end of what is normally fed commercially. In a separate study, laboratory rats were fed 5 and 10 g unprocessed soybean meal 100 g diet. The study durations were 4 wk (rats and dairy cows), 6 wk (broilers) and 10 wk (catfish). Growth, feed conversion (rats, catfish, broilers), fillet composition (catfish), and breast muscle and fat pad weights (broilers) were compared for animals fed the parental and GTS lines. Milk production, milk composition, rumen fermentation and nitrogen digestability were also compared for dairy cows. In all studies, measured variables were similar for animals fed both GTS lines and the parental line, indicating that the feeding value of the two GTS lines is comparable to that of the parental line. These studies support detailed compositional analysis of the GTS seeds, which showed no meaningful differences between the parental and GTS lines in the concentrations of important nutrients and antinutrients. They also confirmed the results of other studies that demonstrated the safety of the introduced protein, a bacterial 5-enolpyruvyl-shikimate-3-phosphate synthase from Agrobacterium sp. strain CP4.
To assess, if and for whom, there are cost savings associated with alternate breast radiotherapy (RT) techniques when compared with the conventional external beam-based whole-breast RT with a boost ...(WBRT-B).
Treatment planning and delivery utilization data were modeled for eight different breast RT techniques: (1) WBRT-B: 60 Gy in 30 fractions; (2) WBRT: 50 Gy in 25 fractions; (3) WBRT-accelerated (AC): 42.5 Gy in 16 fractions; (4) WBRT-intensity-modulated RT (IMRT): 60 Gy in 30 fractions; (5) accelerated partial breast irradiation (APBI)-IC, MammoSite: 34 Gy in 10 twice-daily fractions; (6) APBI-IT, HDR interstitial: 34 Gy in 10 twice-daily fractions; (7) APBI three-dimensional conformal RT (3D-CRT): 38.5 Gy in 10 twice-daily fractions; or (8) APBI-IMRT: 38.5 Gy in 10 twice-daily fractions. Costs incurred by payer (i.e., direct medical costs; 2003 Medicare Fee Schedule) and patient (i.e., direct nonmedical costs; time and travel) were estimated. Total societal costs were then calculated for each treatment approach.
Not all efforts to reduce overall treatment time result in total cost savings. The least expensive partial breast-based RT approaches were the external beam techniques (APBI-3D-CRT, APBI-IMRT). Any reduced cost to patients for the HDR brachytherapy-based APBI regimens were overshadowed by substantial increases in cost to payers, resulting in higher total societal costs; the cost of HDR treatment delivery was primarily responsible for the increased direct medical cost. For the whole breast-based RT approaches, treating without a boost (WBRT) or with WBRT-AC reduced total costs. Overall, WBRT-AC was the least costly of all the regimens, in terms of costs to society; APBI approaches, in general, were favored over whole-breast techniques when only considering costs to patients.
Based on societal cost considerations, WBRT-AC appears to be the preferred approach. If one were to pursue a partial-breast RT regimen to minimize patient costs, it would be more advantageous from a societal perspective to pursue external beam-based approaches such as APBI-3D-CRT or APBI-IMRT in lieu of the brachytherapy-based regimens.
At 5-year follow-up, patients with Paget disease of the breast who were treated with breast-conserving surgery (BCS) and radiotherapy (RT) had excellent results. The current report provides 10- and ...15-year rates of tumor control in the breast, as well as disease-free and overall survival rates following BCS and RT in a cohort of patients with Paget disease presenting without a palpable mass or mammographic density.
Through a collaborative review of patients treated with BCS and RT from seven institutions, 38 cases of Paget disease of the breast presenting without a palpable mass or mammographic density were identified. All patients had pathologic confirmation of typical Paget cells at time of diagnosis. Thirty-six of 38 patients had a minimum follow-up greater than 12 months and constitute the study cohort. Ninety-four percent of patients underwent complete or partial excision of the nipple-areola complex and all patients received a median external beam irradiation dose of 50 Gy (range, 45-54 Gy) to the whole breast. Ninety-seven percent of patients also received a boost to the remaining nipple or tumor bed, a median total dose of 61.5 Gy (range, 50.4-70 Gy).
With median follow-up of 113 months (range, 18-257 months), 4 of 36 patients (11%) developed a first recurrence of disease in the treated breast only. Two of the four recurrences in the breast were ductal carcinoma in situ (DCIS) only and two were invasive with DCIS. Two additional patients had a recurrence in the breast as a component of first failure. Actuarial local control rates for the breast as the only site of first recurrence were 91% at 5 years (95% confidence interval CI, 80-100%) and 87% (95% CI, 75-99%) at both 10 and 15 years. Actuarial local control rates for breast recurrence, as a component of first failure, were 91% (95% CI, 80-100%), 83% (95% CI, 69-97%), and 76% (95% CI, 58-94%) at 5, 10, and 15 years, respectively. No clinical factors were identified as significant predictors for breast recurrence. Five-, 10- and 15-year actuarial rates for survival without disease of 97% (95% CI, 90-100%) and 5-, 10-, and 15-year actuarial rates of overall survival of 93% (95% CI, 84-100%) at 5 years and 90% (95% CI, 78-100%) at 10 and 15 years were reported.
These data confirm excellent rates of local control, disease-free survival, and overall survival at 10 and 15 years following BCS and RT for Paget disease of the breast. This study continues to support the recommendation of local excision and definitive breast irradiation as an alternative to mastectomy in the treatment of patients with Paget disease presenting without a palpable mass or mammographic density.
This analysis was performed to clarify the relationship of young age at diagnosis to the pathologic features of the tumor and prognosis in patients with early-stage breast cancer.
We retrospectively ...analyzed data from 1,398 patients with American Joint Committee on Cancer Staging stage I or II breast cancer treated by breast-conserving therapy between 1968 and 1985. One hundred seven patients were younger than 35 years at the time of diagnosis. The median follow-up duration for the 1,032 survivors was 99 months.
Patients younger than 35 years had a significantly higher overall recurrence rate (P = .002), as well as a greater risk for developing distant metastases (P = .03), when compared with older patients. The cancers in younger patients more commonly showed factors associated with a worse prognosis (including grade 3 histology, lymphatic vessel invasion LVI, necrosis, and estrogen receptor ER negativity) as compared with older patients. In a proportional hazards model that included clinical and treatment-related variables, as well as these pathologic features, age younger than 35 years remained a significant predictor for time to recurrence (relative risk RR, 1.70), time to distant failure (RR, 1.60), and overall mortality (RR, 1.50).
Breast cancer patients younger than 35 years have a worse prognosis than older patients. This difference is only partially explained by a higher frequency of adverse pathologic factors seen in younger patients.
The health of dairy cows given bovine somatotropin (bST) for one lactation was evaluated in 28 commercial herds located in four regions of the United States. At least six herds were in a region and ...at least one herd/ region contained fewer than 60 cows. Cows (n = 1213) were assigned randomly to control or bST groups and were treated beginning in wk 9 to 10 of lactation and every 14 d until dry-off or d 400 of lactation. Management was according to site practices. Cows were observed for health-related signs by farm personnel daily and by the herd veterinarian biweekly. Average 305-d test-day milk yields were 932kg greater for bST-treated cows. Pregnancy rates, days open, twinning, cystic ovaries, or abortions were unaffected by treatments. Supplementation of cows with bST had no effect on total mastitis cases, total days of mastitis, duration of mastitis, or the odds ratio of a cow to develop mastitis. Cows supplemented with bST used more medications for health events other than mastitis. This usage was associated primarily with treatments for disorders of the foot and hock. Supplemented cows had a slight increase in foot disorders. There was no effect of supplementation with bST on culling from the herd or removal from study. Overall, the results confirm that label directions for bST are adequate for safe use under field conditions. All clinical signs observed in this study occur normally in dairy herds and were managed in cows supplemented with bST.
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