Effects of tamoxifen and octreotide LAR on the IGF-system compared with tamoxifen monotherapy.

The insulin-like growth factor (IGF)-system was evaluated in 150 breast cancer patients participating in a randomised phase III trial comparing octreotide pamoate and tamoxifen with tamoxifen+placebo. Alterations in the IGF-system in the two treatment arms and individual changes with respect to outcome were compared. Serum IGF-I and -II, free IGF-I, and insulin-like growth factor binding protein 1-3 (IGFBP1-3) were measured by radioimmmunoassay (RIA)/immunoradiometric assay (IRMA) and IGFBPs by Western ligand blots (WLB) before and during treatment. Combined treatment caused a higher increase in IGFBP-1 and larger suppression of total and free IGF-I, IGF-II, and IGFBP-3 (P<0.01 for all), but less suppression of IGFBP-2 (P<0.05) compared with tamoxifen monotherapy. An increase in IGFBP-2 25% was associated with decreased progression-free survival (PFS) in the total patient population and combined treatment group. Similar response rates and time to progression in the treatment arms suggests moderate suppression of circulating IGF-I has no influence on clinical outcome.

Goserelin versus cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy in premenopausal patients with node-positive breast cancer: The Zoladex Early Breast Cancer Research Association Study.

PURPOSE: Current adjuvant therapies have improved survival for premenopausal patients with breast cancer but may have short-term toxic effects and long-term effects associated with premature menopause. PATIENTS AND METHODS: The Zoladex Early Breast Cancer Research Association study assessed the efficacy and tolerability of goserelin (3.6 mg every 28 days for 2 years; n = 817) versus cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy (six 28-day cycles; n = 823) for adjuvant treatment in premenopausal patients with node-positive breast cancer. RESULTS: Analysis was performed when 684 events had been achieved, and the median follow-up was 6 years. A significant interaction between treatment and estrogen receptor (ER) status was found (P =.0016). In ER-positive patients (approximately 74%), goserelin was equivalent to CMF for disease-free survival (DFS) (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.84 to 1.20). In ER-negative patients, goserelin was inferior to CMF for DFS (HR, 1.76; 95% CI, 1.27 to 2.44). Amenorrhea occurred in more than 95% of goserelin patients by 6 months versus 58.6% of CMF patients. Menses returned in most goserelin patients after therapy stopped, whereas amenorrhea was generally permanent in CMF patients (22.6% v 76.9% amenorrheic at 3 years). Chemotherapy-related side effects such as nausea/vomiting, alopecia, and infection were higher with CMF than with goserelin during CMF treatment. Side effects related to estrogen suppression were initially higher with goserelin, but when goserelin treatment stopped, reduced to a level below that observed in the CMF group. CONCLUSION: Goserelin offers an effective, well-tolerated alternative to CMF in premenopausal patients with ER-positive and node-positive early breast cancer.

The time-course of metastases from breast cancer after mastectomy and breast-conserving surgery with and without isolated local-regional recurrence.

We have examined time intervals between events in 390 metastatic breast cancer (MBC) patients whose distant failure developed within 10 years from initial surgery of Stage I/II disease. All of the patients underwent axillary dissection and mastectomy (n=295) or breast-conserving surgery (BCS, n=95), between 1983 and 1987. Distinctions have been made between distant failure with (n=79) and without (n=311) isolated local-regional recurrence (LRR). The median survival time after first relapse was significantly longer with intrabreast (30 months) and chest wall (24 months) than with distant relapse (15 months), but with axillary (17 months) or with supraclavicular (17 months) relapse survival was similar. The delay between LRR and distant metastasis was shorter with axillary (7 months) and supraclavicular (9 months) than with breast (20 months) and chest wall (12 months) recurrences. The median postmetastatic survival time by site of first relapse was significantly shorter with supraclavicular (6 months) and axillary (9 months) than with distant site relapse (15 months) but with intrabreast (12 months) or with chest wall (11 months) recurrence survival was similar. In MBC, regional recurrences are associated with a shorter interval between events than with local recurrences. The shortened intervals for patients with regional recurrence suggest that metastases existed at the time of initial surgery. The question of whether prevention of local or regional recurrence or both improves cause-specific survival after mastectomy or BCS needs to be answered in randomized studies.

Postirradiation angiosarcoma of the chest wall and breast: issues of radiogenic origin, diagnosis and treatment in two cases.

The authors report two cases of postradiation angiosarcoma (AS) among 5,100 breast cancer patients treated in the period 1980-1994 at the National Institute of Oncology, Budapest. Relevant data in the literature is also reviewed to analyze the questions of radiogenic origin, diagnosis and treatment. Secondary AS occurred in these cases in a previously irradiated field after a 6- and 8-year latency period, respectively. Detailed histopathological and immunohistochemical examinations from the biopsy specimens confirmed the diagnosis as AS. The first patient was treated successfully with radical surgery. The second patient, with unresectable AS, died of rapid local progression within 4 months. The incidence of chest wall and breast AS after radiotherapy was found to be 0.46 per 1,000 in our patient population, which means an estimated odds ratio of 2.9 for secondary AS. Patients treated with radiotherapy for primary breast cancer are at higher risk for developing secondary AS compared to the healthy population. An etiological relationship between radiotherapy and subsequent AS of the chest wall and breast is likely, but still controversial. Initial radical surgery is the only effective treatment for achieving long-term survival. These very rare cases deserve special attention due to the atypical clinical appearance, difficulties of differential diagnosis and poor prognosis.

Uric acid in a single urine sample from neonates with perinatal hypoxia.

In a referral neonatal intensive care unit, PaO2 values of 40 newborn infants were compared with the serum and urinary uric acid levels. The latter was estimated from the first urine obtained after admission. A significant inverse correlation was found between PaO2 and serum uric acid concentration and between PaO2 and urinary uric acid per creatinine ratio, but no correlation was seen between PaO2 and urinary uric acid concentration. The urinary uric acid per creatinine ratio was determined on the 1st, 2nd and 5th days of life in 27 normal prematures, 28 hypoxic prematures, 23 normal full-term infants and 25 hypoxic full-term neonates. Significantly higher values were obtained in both hypoxic groups on the 1st day, and in hypoxic prematures even on the 2nd day. Although creatinine as a reference substance is regarded as unreliable in the neonatal period, if a single urine sample is only available, determination fo the uric acid per creatinine ratio seems to be warranted, since higher values may retrospectively point to hypoxia.