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 amenorrhea.

Differential efficacy of three cycles of CMF followed by tamoxifen in patients with ER-positive and ER-negative tumors: long-term follow up on IBCSG Trial IX.

BACKGROUND: The benefit of adjuvant chemotherapy in postmenopausal patients with estrogen receptor (ER)-positive lymph node-negative breast cancer is being reassessed. PATIENTS AND METHODS: After stratification by ER status, 1669 postmenopausal patients with operable lymph node-negative breast cancer were randomly assigned to three 28-day courses of 'classical' CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy followed by tamoxifen for 57 months (CMF→tamoxifen) or to tamoxifen alone for 5 years. RESULTS: ERs were positive in 81% of tumors. At a median follow-up of 13.1 years, patients with ER-positive breast cancers did not benefit from CMF [13-year disease-free survival (DFS) 64% CMF→tamoxifen, 66% tamoxifen; P = 0.99], whereas CMF substantially improved the prognosis of patients with ER-negative breast cancer (13-year DFS 73% versus 57%, P = 0.001). Similarly, breast cancer-free interval (BCFI) was identical in the ER-positive cohort but significantly improved by chemotherapy in the ER-negative cohort (13-year BCFI 80% versus 63%, P = 0.001). CMF had no influence on second nonbreast malignancies or deaths from other causes. CONCLUSION: CMF is not beneficial in postmenopausal patients with node-negative ER-positive breast cancer but is highly effective within the ER-negative cohort. In the future, other markers of chemotherapy response may define a subset of patients with ER-positive tumors who may benefit from adjuvant chemotherapy.

Adverse prognostic value of peritumoral vascular invasion: is it abrogated by adequate endocrine adjuvant therapy? Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy for early breast cancer.

BACKGROUND: Peritumoral vascular invasion (PVI) may assist in assigning optimal adjuvant systemic therapy for women with early breast cancer. PATIENTS AND METHODS: Patients participated in two International Breast Cancer Study Group randomized trials testing chemoendocrine adjuvant therapies in premenopausal (trial VIII) or postmenopausal (trial IX) node-negative breast cancer. PVI was assessed by institutional pathologists and/or central review on hematoxylin-eosin-stained slides in 99% of patients (analysis cohort 2754 patients, median follow-up >9 years). RESULTS: PVI, present in 23% of the tumors, was associated with higher grade tumors and larger tumor size (trial IX only). Presence of PVI increased locoregional and distant recurrence and was significantly associated with poorer disease-free survival. The adverse prognostic impact of PVI in trial VIII was limited to premenopausal patients with endocrine-responsive tumors randomized to therapies not containing goserelin, and conversely the beneficial effect of goserelin was limited to patients whose tumors showed PVI. In trial IX, all patients received tamoxifen: the adverse prognostic impact of PVI was limited to patients with receptor-negative tumors regardless of chemotherapy. CONCLUSION: Adequate endocrine adjuvant therapy appears to abrogate the adverse impact of PVI in node-negative disease, while PVI may identify patients who will benefit particularly from adjuvant therapy.

Postoperative atrial tachyarrhythmias in patients undergoing coronary artery bypass graft surgery without cardiopulmonary bypass: a role for intraoperative magnesium supplementation.

OBJECTIVE: To determine if intraoperative magnesium supplementation would be associated with a reduction in postoperative atrial tachyarrhythmias (POAT) in patients undergoing coronary artery bypass grafting (CABG) surgery without cardiopulmonary bypass (off-pump CABG surgery). DESIGN: Retrospective study. SETTING: University Medical Center. PARTICIPANTS: Patients who had undergone off-pump CABG surgery (n = 124). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The charts of 124 patients who had undergone off-pump CABG surgery (64 by anterior thoracotomy and 60 by median sternotomy) were retrospectively reviewed. Demographic data and perioperative care were recorded and compared among patients who did and did not experience POAT and among patients who did and did not receive intraoperative magnesium supplementation. Logistic regression analysis was used to assess the association between magnesium supplementation and incidence of POAT, controlling for other covariables. Of the 124 patients, 16 had a prior history of atrial or ventricular arrhythmias and/or were receiving antiarrhythmic medications. Medical records of the remaining 108 patients were reviewed. Twenty-four patients (22%) had POAT. Forty-two patients (39%) received intraoperative magnesium. In patients receiving intraoperative magnesium, the incidence of POAT was significantly decreased (12% v 29%; p = 0.03). In these patients, initial postoperative serum magnesium was significantly higher (2.37 mEq/L v 1.86 mEq/L; p < 0.01). In patients not receiving intraoperative magnesium, 35% had hypomagnesemia (serum magnesium < 1.8 mEq/L) compared with 9% of patients receiving magnesium (p < 0.01). Patients who received intraoperative magnesium and beta-adrenergic blockers had a lower incidence of POAT (5%) than patients who received only one (19%) or neither (33%) (p < 0.05). CONCLUSIONS: Intraoperative magnesium supplementation is associated with a decrease in POAT after off-pump CABG surgery. The combination of a beta-blocker and magnesium may reduce POAT further. It is recommended that intraoperative magnesium supplementation be part of the care of patients undergoing off-pump CABG surgery.