Comparative analysis of micrometastasis to the bone marrow and lymph nodes of node-negative breast cancer patients receiving no adjuvant therapy.
OBJECTIVE
In node-negative patients, of whom up to 30% will recur within 5 years after diagnosis, markers are still needed that identify patients at high enough risk to warrant further adjuvant treatment. In the present study we analyzed whether a correlation exists between microscopic tumor cell spread to bone marrow and to lymph nodes and attempted to determine which route is clinically more important.


METHODS
According to a prospective design, bone marrow aspirates and axillary lymph nodes of level I (n = 1,590) from 150 node-negative patients with stage I or II breast cancer were analyzed immunocytochemically with monoclonal anticytokeratin (CK) antibodies. We investigated associations with prognostic factors and the effect of micrometastasis on patients' prognosis.


RESULTS
CK-positive cells in bone marrow aspirates were present in 44 (29%) of 150 breast cancer patients, whereas only 13 patients (9%) had such positive findings in lymph nodes; simultaneous microdissemination to bone marrow and lymph nodes was seen in merely two patients. No correlation of bone marrow micrometastases with other risk factors was assessed. Reduced 4-year distant disease-free and overall survival were each associated with a positive bone marrow finding (P =.032 and P =.014, respectively) but not with lymph node micrometastasis. Multivariate analysis revealed an independent prognostic effect of bone marrow micrometastasis on survival, with a hazards ratio of 6.1 (95% confidence interval, 1.2 to 31.3) for cancer-related death (P =.031) in our series.


CONCLUSIONS
Immunocytochemical detection of micrometastatic cells in bone marrow but not in lymph nodes is an independent prognostic risk factor in node-negative breast cancer that may have implications for surgery and stratification into adjuvant therapy trials.
Braun
S
S
I. Frauenklinik and Department of Gynecological Pathology, Klinikum Innenstadt, Ludwig-Maximilians-University, München, Gemany. stephan.braun@lrz.tum.de
Cevatli
B S
BS
Assemi
C
C
Janni
W
W
Kentenich
C R
CR
Schindlbeck
C
C
Rjosk
D
D
Hepp
F
F
D019046:Bone Marrow Neoplasms / Q000556:secondary* / Q000601:surgery; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D018714:Radiotherapy, Adjuvant; D012307:Risk Factors; D016019:Survival Analysis