A B S T R A C T PurposeTo investigate the activity of letrozole plus/minus oral metronomic cyclophophamide as primary systemic treatment (PST) in elderly breast cancer patients. MethodsOne hundred fourteen consecutive elderly women with T2-4 N0-1 and estrogen receptorpositive breast cancer were randomly assigned to primary letrozole therapy (2.5 mg daily for 6 months) or a combination of letrozole plus oral cyclophosphamide (50 mg/daily for 6 months) in an open-labeled, randomized phase II trial. Tumor response was assessed clinically, and tumor Ki67 index and vascular endothelial growth factor (VEGF) -A levels were measured before and after treatment. ResultsOverall response rate was 71.9% (95% CI, 60.0 to 83.8) in the 57 patients randomly assigned to receive primary letrozole and 87.7% (95% CI, 78.6 to 96.2) in the 57 patients randomly assigned to receive letrozole plus cyclophosphamide. The difference in activity between treatment arms was predominantly confined to patients with ductal histology. There was a significantly greater suppression of Ki67 and VEGF-A expression in the letrozole/cyclophosphamide-treated group than in the letrozole-treated group, leading to lower Ki67 and VEGF expression at post-treatment residual histology (P ϭ .03 and P ϭ .002, respectively). ConclusionBoth letrozole and letrozole plus cyclophosphamide treatments appeared active as PST in elderly breast cancer patients. Metronomic scheduling of cyclophosphamide may have an antiangiogenetic effect and the combination of letrozole plus cyclophosphamide warrants testing in a randomized phase III trial.

Given two (positive) equivalence relations ~1, ~2 on the set ω of natural numbers, we say that ~1 is m-reducible to ~2 if there exists a total recursive function h such that for every x, y ∈ ω, we have x ~1y iff hx ~2hy. We prove that the equivalence relation induced in ω by a positive precomplete numeration is complete with respect to this reducibility (and, moreover, a “uniformity property” holds). This result allows us to state a classification theorem for positive equivalence relations (Theorem 2). We show that there exist nonisomorphic positive equivalence relations which are complete with respect to the above reducibility; in particular, we discuss the provable equivalence of a strong enough theory: this relation is complete with respect to reducibility but it does not correspond to a precomplete numeration.From this fact we deduce that an equivalence relation on ω can be strongly represented by a formula (see Definition 8) iff it is positive. At last, we interpret the situation from a topological point of view. Among other things, we generalize a result of Visser by showing that the topological space corresponding to a partition in e.i. sets is irreducible and we prove that the set of equivalence classes of true sentences is dense in the Lindenbaum algebra of the theory.

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