Twenty-year results of the Naples GUN randomized trial: predictive factors of adjuvant tamoxifen efficacy in early breast cancer.

PURPOSE: Tamoxifen (TAM) is increasingly administered to new early breast cancer patients. Because it is not devoid of toxic effects, we studied factors potentially predictive of its efficacy. EXPERIMENTAL DESIGN: From 1978 to 1983, 433 patients were enrolled in the GUN randomized trial: 206 were assigned to TAM versus 227 controls (no-TAM). Premenopausal patients with axillary lymph node involvement (60 TAM versus 65 no-TAM) also received nine CMF cycles. Eight biological markers were retrospectively assayed for most patients: estrogen; progesterone; prolactin receptors (PrlRs); microvessel count (MVC); S-phase fraction; tumor ploidy; epidermal growth factor receptor (EGFR); and HER2. We performed a multivariate test of the TAM/covariate interactions to establish whether these variables predicted for TAM efficacy. Estimates of the TAM effect were expressed as hazard ratio (HR) of death of TAM over no-TAM patients with 95% confidence intervals (95% CIs). RESULTS: At a median follow-up of 15 years, PrlRs, MVC, S-phase fraction, ploidy, and EGFR did not influence TAM efficacy. Differently, HER2 had an overall significant predictive effect: HR = 0.59 (95% CI: 0.40-0.87) in HER2-negative subjects versus HR = 1.09 (95% CI: 0.63-1.87) in HER2-positive subjects (interaction test: P = 0.04). The predictive effect of HER2 was also evident in the subgroup of patients with steroid receptor-positive tumors (HER2 positive: HR = 1.33, 95% CI: 0.70-2.51; HER2 negative: HR = 0.73, 95% CI: 0.47-1.14). CONCLUSIONS: With the statistical power of the present randomized trial, S-phase, ploidy, EGFR, PrlR, and MVC do not seem to predict for TAM efficacy. Conversely, our data support the hypothesis that tumors overexpressing HER2 might not benefit from adjuvant TAM.

Radiation therapy following surgery for localized breast cancer: outcome prediction by classical prognostic factors and approximated genetic subtypes.

The purpose of this study was to evaluate the outcome prediction power of classical prognostic factors along with surrogate approximation of genetic signatures (AGS) subtypes in patients affected by localized breast cancer (BC) and treated with postoperative radiotherapy. We retrospectively analyzed 468 consecutive female patients affected by localized BC with complete immunohistochemical and pathological information available. All patients underwent surgery plus radiotherapy. Median follow-up was 59 months (range, 6-132) from the diagnosis. Disease recurrences (DR), local and/or distant, and contralateral breast cancer (CBC) were registered and analyzed in relation to subtypes (luminal A, luminal B, HER-2, and basal), and classical prognostic factors (PFs), namely age, nodal status (N), tumor classification (T), grading (G), estrogen receptors (ER), progesterone receptors and erb-B2 status. Bootstrap technique for variable selection and bootstrap resampling to test selection stability were used. Regarding AGS subtypes, HER-2 and basal were more likely to recur than luminal A and B subtypes, while patients in the basal group were more likely to have CBC. However, considering PFs along with AGS subtypes, the optimal multivariable predictive model for DR consisted of age, T, N, G and ER. A single-variable model including basal subtype resulted again as the optimal predictive model for CBC. In patients bearing localized BC the combination of classical clinical variables age, T, N, G and ER was still confirmed to be the best predictor of DR, while the basal subtype was demonstrated to be significantly and exclusively correlated with CBC.

Adjuvant FOLFOX-4 in patients with radically resected gastric cancer: Tolerability and prognostic factors.

The aim of the present study was to evaluate the toxicity and efficacy of the FOLFOX-4 regimen as adjuvant chemotherapy in patients with gastric cancer after radical surgery. Fifty-four patients (1 stage Ib, 6 stage II, 22 stage IIIa, 14 stage IIIb and 11 stage IV) received 8-12 cycles of FOLFOX-4 (oxaliplatin 85 mg/m(2), Day 1; leucovorin 100 mg/m(2) i.v., Days 1 and 2; 5-fluorouracil 400 mg/m(2) i.v. bolus, Days 1 and 2 and 600 mg/m(2) in 22 h i.v. continuous infusion, Days 1 and 2; every 14 days). Toxicity was recorded at each cycle according to the National Cancer Institute Common Toxicity Criteria. Disease-free (DFS) and overall survival (OS) were calculated according to the Kaplan-Meier method. Thirty-eight patients (70.4%) completed the prescribed number of cycles of chemotherapy. The toxicity was mild. Grade 3-4 neutropenia occurred in 57% of patients, thrombocytopenia and anemia in 2% of cases. Peripheral neuropathy was experienced by 46% of the patients (grade 4 in 2% of cases). Five patients experienced grade 3 gastrointestinal toxicity. After a median follow-up of 33.1 months, 17 patients relapsed and 17 succumbed to the disease. The mean observed DFS and OS were 49.7 months (range 40.7-58.8) and 57.9 months (range 49.6-66.2), respectively. At univariate analysis, females and patients who had received <8 cycles of chemotherapy had a significantly worse probability of DFS and OS. The Cox model showed gender to be independent of the factors affecting DFS. Adjuvant FOLFOX-4 is feasible and well-tolerated in patients radically resected for gastric cancer. Receiving <4 months of adjuvant FOLFOX-4 could be detrimental to prognosis.