Cytokeratin positivity in bone marrow cells as predictor of onset of bone metastases in patients with advanced breast cancer.

Objective: Despite screening programs, advances in therapeutic approaches and understanding the molecular bases of cancer biology, breast cancer (BC) remains the first cause of cancer death in women aged over 50 years. Bone is one of the most common sites of metastasis in BC patients, and the presence of disseminated tumor cells in bone marrow (BM) seems to have a strong independent prognostic value. The aim of this study was to investigate whether the immunocytochemical detection of disseminated tumor cells in BM can be considered as predictor of onset of bone metastases in patients with advancer BC. Material and Methods: A group of 21 surgically treated women (median age 54, range 47–68 years) with advanced (stage II-III) BC and no evidence of distant metastases at first diagnosis were followed-up for at least 24 months. All patients underwent whole bone scan or 18 F-FDG-PET for inclusion in the study, together with a baseline BM aspirate from the posterior iliac crest. The cells were stained with a monoclonal antibody against cytokeratin (CK). A according to the ISHAGE guidelines, CK+cells were scored as tumor cells. Six out of 21 (28.6 %) patients (cases) developed bone metastases, while 15 (controls) had no evidence of distant metastases. Results: Risk ratio (RR), 95 % confidence interval (CI), and the relative p-value (p) using Fisher exact test between cases and controls were calculated. The following parameters have been considered: age <50 years (RR=2.0, 95 %CI 0.80-4.98, p=0.18), estrogen receptor negativity (ER-) (RR=2.2, 95 %CI 0.68-7.11, p=0.11), human epidermal growth factor-2 (HER2) positivity (RR=1.66, 95 %CI 0.36-7.60, p=0.44), more than 5 involved axillary lymph nodes (>5 AN+)(RR=2.5, 95 %CI 0.91-6.87, p=0.11), and CK+(RR=3.21, 95 %CI 1.25-7.78, p=0.02). Conclusion: The presence of CK+cells in the BM specimen should be considered a strong predictor (p<0.05) of onset of bone metastases in patients with stage II-III BC, while >5 AN+and ER- are weak predictors.