S. Braun et al., Cytokeratin-positive cells in the bone marrow and survival of patients with stage I, II, or III breast cancer., N ENG J MED, 342(8), 2000, pp. 525-533
Citations number
45
Categorie Soggetti
General & Internal Medicine","Medical Research General Topics
Background: Cytokeratins are specific markers of epithelial cancer cells in
bone marrow. We assessed the influence of cytokeratin-positive micrometast
ases in the bone marrow on the prognosis of women with breast cancer.
Methods: We obtained bone marrow aspirates from both upper iliac crests of
552 patients with stage I, II, or III breast cancer who underwent complete
resection of the tumor and 191 patients with nonmalignant disease. The spec
imens were stained with the monoclonal antibody A45-B/B3, which binds to an
antigen on cytokeratins. The median follow-up was 38 months (range, 10 to
70). The primary end point was survival.
Results: Cytokeratin-positive cells were detected in the bone marrow specim
ens of 2 of the 191 control patients with nonmalignant conditions (1 percen
t) and 199 of the 552 patients with breast cancer (36 percent). The presenc
e of occult metastatic cells in bone marrow was unrelated to the presence o
r absence of lymph-node metastasis (P = 0.13). After four years of follow-u
p, the presence of micrometastases in bone marrow was associated with the o
ccurrence of clinically overt distant metastasis and death from cancer-rela
ted causes (P<0.001), but not with locoregional relapse (P = 0.77). Of 199
patients with occult metastatic cells, 49 died of cancer, whereas of 353 pa
tients without such cells, 22 died of cancer-related causes (P<0.001). Amon
g the 301 women without lymph-node metastases, 14 of the 100 with bone marr
ow micrometastases died of cancer-related causes, as did 2 of the 201 witho
ut bone marrow micrometastases (P<0.001). The presence of occult metastatic
cells in bone marrow, as compared with their absence, was an independent p
rognostic indicator of the risk of death from cancer (relative risk, 4.17;
95 percent confidence interval, 2.51 to 6.94; P<0.001), after adjustment fo
r the use of systemic adjuvant chemotherapy.
Conclusions: The presence of occult cytokeratin-positive metastatic cells i
n bone marrow increases the risk of relapse in patients with stage I, II, o
r III breast cancer. (N Engl J Med 2000;342:525-33.) (C)2000, Massachusetts
Medical Society.