Sequential estrogen receptor determinations from primary breast cancer and at relapse: prognostic and therapeutic relevance. The International Breast Cancer Study Group (formerly Ludwig Group).

We retrospectively evaluated 401 selected patients who had estrogen receptor (ER) assays both at primary surgery and at relapse in an accessible site to determine the clinical relevance of the subsequent ER determination. The median time between ER assessments was 27 months (range: 2-122 months). The median follow-up time from diagnosis was 6 years (range: 2-12 years). For patients with ER+ tumors at primary diagnosis, 29% (76/261) had ER- tumors at relapse, while for ER- primaries, the conversion rate was 33% (46/140). Conversions from ER+ to ER- occurred more often when the time interval between assays was less than one year (p = 0.004), while conversions from ER- to ER+ tended to occur late (beyond three years; p = 0.0003). Treatments received between assays (usually adjuvant therapy) had only a slight influence on ER status conversion. Post-relapse survival was poor for patients who had the biopsy accessible recurrence within one year; an expression of the aggressive nature of the disease. Among patients whose accessible relapse was beyond one year, those with ER- primaries who converted to ER+ had a longer survival than those whose recurrence was classified again as ER- (p = 0.006). This group of patients with ER- primaries who recurred beyond one year with an ER+ tumor in an accessible site represented 29% (40/140) of all patients with ER- primaries and had an estimated overall survival rate of more than 60% at 6 years from the accessible relapse. ER determination upon relapse within one year has very little clinical relevance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Human temperature regulation during cycling with moderate leg ischaemia

The effect of graded ischaemia in the legs on the regulation of body temperature during steady-state exercise was investigated in seven healthy males. It was hypothesised that graded ischaemia in the working muscles increases heat storage within the muscles, which in turn potentiates sweat secretion during exercise. Blood perfusion in the working muscles was reduced by applying a supra-atmospheric pressure (+6.6 kPa) around the legs, which reduced maximal working capacity by 29%. Each subject conducted three separate test trials comprising 30 min of steady-state cycling in a supine position. Exercise with unrestricted blood flow (Control trial) was compared to ischaemic exercise conducted at an identical relative work rate (Relative trial), as well as at an identical absolute work rate (Absolute trial); the latter corresponding to a 20% increase in relative workload. The average (SD) increases in both the rectal and oesophageal temperatures during steady-state cycling was 0.3 (0.2)°C and did not significantly differ between the three trials. The increase in muscle temperature was similar in the Control (2.7 (0.3)°C) and Absolute (2.4 (0.7)°C) trials, but was substantially lower (P<0.01) in the Relative trial (1.4 (0.8)°C). Ischaemia potentiated (P<0.01) sweating on the forehead in the Absolute trial (24.2 (7.3) g m^–2 min^–1) compared to the Control trial (13.4 (6.2) g m^–2 min^–1), concomitant with an attenuated (P<0.05) vasodilatation in the skin during exercise. It is concluded that graded ischaemia in working muscles potentiates the exercise sweating response and attenuates vasodilatation in the skin initiated by increased core temperature, effects which may be attributed to an augmented muscle metaboreflex.     

Menstrual cycle and timing of breast surgery in premenopausal node-positive breast cancer: Results of the International Breast Cancer Study Group (IBCSG) Trial VI

Purpose: It has been postulated that breast cancer surgery performedduring the follicular phase of the menstrual cycle is associated with pooreroutcome.Patients and methods: We tested this hypothesis by evaluatingdisease-free survival (DFS) for 1033 premenopausal patients who receiveddefinitive surgery either during the follicular phase (n = 358) or theluteal phase (n = 675). All patients were enrolled in a randomized trialconducted between July 1986 and April 1993. All had node positive breastcancer and randomization was stratified by estrogen receptor (ER) status.All patients received at least three cycles of adjuvant cyclophosphamide,methotrexate, and 5-fluorouracil (CMF). The median follow-up was 60 months.Results: Patients who underwent definitive surgery for breast cancer inthe follicular phase had a slightly worse disease-free survival than thoseoperated on during the luteal phase (five-year DFS percentage: 53%versus 58%; hazard ratio, 1.13; 95% confidence interval (CI),0.94–1.38; P = 0.20). The effect was significantly greater for thesubpopulation of 300 patients with ER-negative primaries (P = 0.02interaction effect; five-year DFS percentages 42% vs. 59%;hazard ratio 1.60; 95% CI, 1.12–2.25; P = 0.008). The effect oftiming of surgery diminished for analyses based on lesser surgicalprocedures, e.g., excisional biopsies. In particular, no effect of timingwas observed for fine needle aspiration procedures.Conclusions: Surgical procedures which are more extensive than a fineneedle aspiration biopsy might be associated with worse prognosis if conductedduring the follicular phase of the menstrual cycle. This phenomenon was seenpredominantly for high risk breast cancer with low levels or no estrogenreceptors in the primary tumor.     

A trace element preparation increases antitumor activity in mice

A trace element preparation (Béres Drops Plus, BDP) produced immunomodulatory effects in previous in vitro and in vivo experiments. Here, C57B1/6 inbred mice were transplanted with either Lewis lung tumor or with B16 melanoma. BDP was given intraperitoneally a. before transplantation; b. after transplantation or c. after the removal of the primary tumor. As a result, BDP pretreatment could slow down the tumor progression by decreasing the number and the volume of metastases as well as the proportion of mice with metastases without influencing the growth of the primary tumors. Furthermore, BDP treatment improved the immunological activity of the tumor-bearing host, too. These preliminary data suggest that the parenteral administration of the practically non-toxic BDP could help to control tumor progression in experimental models.     

Timing of CMF chemotherapy in combination with tamoxifen in postmenopausal women with breast cancer: role of endocrine responsiveness of the tumor.

BACKGROUND: Controversy persists about whether chemotherapy benefits all breast cancer patients. PATIENTS AND METHODS: In the International Breast Cancer Study Group (IBCSG) trial VII, 1212 postmenopausal patients with node-positive disease were randomized to receive tamoxifen for 5 years or tamoxifen plus three concurrent courses of cyclophosphamide, methotrexate and 5-fluorouracil ('classical' CMF) chemotherapy, either early, delayed or both. In IBCSG trial IX, 1669 postmenopausal patients with node-negative disease were randomized to receive either tamoxifen alone or three courses of adjuvant classical CMF prior to tamoxifen. Results were assessed according to estrogen receptor (ER) content of the primary tumor. RESULTS: For patients with node-positive, ER-positive disease, adding CMF either early, delayed or both reduced the risk of relapse by 21% (P=0.06), 26% (P=0.02) and 25% (P=0.02), respectively, compared with tamoxifen alone. There was no difference in disease-free survival when CMF was given prior to tamoxifen in patients with node-negative, ER-positive tumors. CONCLUSIONS: CMF given concurrently (early, delayed or both) with tamoxifen was more effective than tamoxifen alone for patients with node-positive, endocrine-responsive breast cancer, supporting late administration of chemotherapy even after commencement of tamoxifen. In contrast, sequential CMF and tamoxifen for patients with node-negative, endocrine-responsive disease was ineffective.     

Increased Risk of Infections with Anti-TNF Agents in Patients with Crohn’s Disease After Elective Surgery: Meta-Analysis

Digestive Diseases and Sciences - Postoperative complication rates in patients with inflammatory bowel disease (IBD) receiving preoperative biologics have been analyzed without considering the...     

A 44-year-old man with bilateral eyelid swelling

Swollen eyelids are commonly ascribed to allergic conjunctivitis, contact dermatitis, eczema, angioedema, or acute sinusitis. The differential diagnosis extends to thyroid eye disease; blepharitis; Sj?gren's syndrome; Churg-Strauss vasculitis; Wegener's granulomatosis; Gleich syndrome; orbital and ocular lymphoid hyperplasia or adnexal lymphoma; idiopathic orbital inflammatory disease/idiopathic sclerosing orbital inflammation; rarely, orbital parasitosis; and IgG4-related diseases. The likely diagnosis proceeds from the more to the less common in patients without a history of allergy or infection. Both ocular lymphoid hyperplasia and ocular adnexal lymphoma must be considered in the differential diagnosis of persistent disease, and neither of these entities can be recognized or differentiated from one another clinically or radiologically. Early diagnosis is essential because therapy may consist of frequent follow-up and/or active intervention. Outcomes in patients treated early and appropriately are often favorable.     

The International (Ludwig) Breast Cancer Study Group Trials I-IV: 15 years follow-up

BACKGROUND: Adjuvant systemic therapy prolongs disease-free and overallsurvival in both pre- and postmenopausal patients. Availabledata shown benefit from multi-agent chemotherapy, prolongedtamoxifen treatment, and ovarian ablation, and that the combinationof chemo- and endocrine therapy might be advantageous. In 1978the International (Ludwig) Breast Cancer Study Group (IBCSG)initiated four complementary randomized controlled clinicaltrials to evaluate the roles of chemo-endocrine combinationsor endocrine therapy alone in specific populations defined byrisk (for pre- and perimenopausal patients) or by age (for postmenopausalpatients). The results at 10 and 13 years' median follow-upfor these trials are summarized in this report and are comparedto those of the Overview meta-anal-ysis with regard to chemo-endocrineor endocrine therapy combinations. Furthermore, types of firstrelapses by sites and second malignant diseases are reported. PATIENTS AND METHODS: 1601 evaluable patients with node positive disease were includedinto the studies I–IV. In Trial I (491 premenopausal patientswith 1–3 positive axillary nodes) we studied the additionof low-dose continuous prednisone (p) to a cyclophosphamide-methotrexate-fluorouracil(CMF) combination. In Trial n 327 premenopausal patients withfour or more positive axillary nodes were randomized to oneyear CMFp or to a surgical oophorectomy followed by CMFp. InTrial III (463 postmenopausal patients 65 years old or younger),combined chemoendocrine therapy (one year of CMFp plus tamoxifen(T)) was compared to endocrine therapy (1 year of p + T) orto surgery alone. In Trial IV 320 postmenopausal patients 66to 80 years old were treated either by surgery alone or by surgeryfollowed by 1 year prednisone and tamoxifen. RESULTS: In Trial I the addition of prednisone allowed a higher doseof cytotoxics to be administered compared with CMF alone. Despitethis increased dose intensity, 13-year disease-free survival(DFS) and overall survival (OS) were similar for the two treatmentgroups (49% vs. 52% DFS, 59% vs. 65% OS for CMFp vs. CMF). InTrial II the addition of surgical oophorectomy to CMFp yieldedan improved outcome which approached statistical significancefor the subset of 107 patients known to have estrogen receptor-positivetumors (DFS, 23% vs. 15%, p     

Routine tests during follow-up of patients after primary treatment for operable breast cancer

Background: Follow-up tests for patients after diagnosis andprimary treatment of breast cancer are routinely performed.However, the usefulness of these follow-up parameters remainsunclear. We determined the yield of a variety of blood testsused to detect the presence of overt metastatic disease Methods: 4105 patients enrolled in International (Ludwig) BreastCancer Study Group (IBCSG) randomized clinical trials from 1978to 1985 were analyzed for abnormal or equivocal findings insix routine blood tests obtained every 3 months for the firsttwo years, every six months for years 3–5 and yearly thereafter.The relationship of test results to the occurrence of overtmetastatic disease was evaluated. The relapses were categorizedas follows in order to estimate the yield of the different testsfor relevant sites of metastases: any breast cancer relapse,bone ± other; liver ± other Results: Alkaline phosphatase alone was abnormal in a high proportionof patients with either bone metastases, liver metastases, orboth. SGOT and gamma-GT were also sensitive for patients withliver metastases. Bilirubin, serum calcium, and serum creatininewere relatively insensitive indicators of relapse. Abnormaltest results were reported sometime during a patient's disease-freeperiod for 3% to 6% of patients, depending on the test Conclusions: Alkaline phosphatase was the most effective bloodtest to distinguish patients with relapse from those withoutrelapse. It is inexpensive and its yield is relatively highfor predicting liver and bone metastases. The routine use ofthe other tests analyzed to detect metastases was not justified breast cancer, follow-up, evaluation, routine tests