Angiogenesis, as assessed by microvessels, has been a common prognostic ind
icator for breast cancer in the last decade. However, the significance of a
ngiogenesis remains controversial. This is a retrospective study of 377 Jap
anese patients selected from 663 breast cancer patients operated on between
1971 and 1987. To evaluate an objective method to quantify microvessel den
sity in angiogenesis, we employed average microvessel count (AMC) per squar
e millimeter. We investigated five factors: angiogenesis, lymph-node status
(n), clinical tumor size (T), histological grade (HG), and tumor necrosis
(TN), followed for a median of 10 years. Sixty-seven patients (17.8%) had r
ecurrence and 54 patients (14.3%) died of breast cancer. Univariate analysi
s showed that n, T, HG, and AMC (P = 0.0020) were significantly predictive
of 20-year relapse-free survival (RFS). n, T, and HG were significantly ass
ociated with 20-year overall survival (OS) but AMC was borderline significa
nt (P = 0.0630). Multivariate analysis for RFS and OS showed that n, T, HG,
and AMC (P < 0.0001, P = 0.0033, respectively) were all significant and in
dependent prognostic factors. When stratified by T or n, a significant impa
ct of AMC on RFS or OS was seen both in patients with T2 and T3 carcinomas
or in node-negative patients, but not in T1 or node-positive patients. Thus
, we can confirm angiogenesis as a significant independent prognostic facto
r associated with long-term survival in Japanese breast cancer patients, es
pecially in node-negative patients and in patients with T2 and T3 carcinoma
s.