Prediction of early relapse in patients with operable breast cancer by detection of occult bone marrow micrometastases.

Abstract

We used monoclonal antibodies to identify occult micrometastases in the bone marrow of 49 patients with operable (stage I and II) breast carcinoma. Follow-up (mean, 29 months; median, 30 months) revealed that 12 patients recurred. The presence of bone marrow micrometastases (BMM) was significantly associated with early recurrence (P less than .04). The estimated 2-year recurrence rate for patients with no BMM detected (BMM-) was 3%; in patients with BMM, the 2-year recurrence rate was 33%. When BMM and axillary lymph node (LN) status were combined, groups of patients at low risk (LN-, BMM-; 2-year recurrence rate, 0%) and high risk (LN+, BMM+; 2-year recurrence rate, 42%) for early recurrence were identified. Bone marrow tumor burden was related to early recurrence. Among patients with BMM, those who did not recur had on average fewer extrinsic cells in their marrow than those who recurred (15 v 43 cells, respectively). Multivariate analysis comparing BMM, LN+ versus LN-, and tumor size (less than or equal to 2 cm v greater than 2 cm) revealed no factor independently associated with early recurrence. Peripheral tumor burden of BMM (0 or less than 10 extrinsic cells v greater than or equal to 10 extrinsic cells) was the only independent predictor of early recurrence (P less than .003). In conjunction with conventional prognostic factors, particularly axillary LN status, evaluation for BMM might be used to stratify patients for adjuvant treatment programs. Because this pilot study involved few patients with short-term follow-up, the results should be interpreted with caution. The examination of bone marrow for micrometastases remains an experimental procedure; the clinical usefulness of the test will be established through larger studies with long-term follow-up.

Occult axillary node metastases in breast cancer: their detection and prognostic significance

“…We shall be examining the associations of such factors in these patients in the near future. Detection of metastatic tumour cells in bone marrow of breast cancer patients is now also feasible and may have prognostic significance (Cote et al, 1991;Dearnaley et al, 1991), and could also be combined into a risk index.…”

A quantitative reverse transcriptase polymerase chain reaction-based assay to detect carcinoma cells in peripheral blood

“…Second, in the setting of autologous bone marrow transplantation (ABMT) or peripheral stem cell reinfusion after high-dose chemotherapy, contamination of the reinfused bone marrow or stem cell population with tumour cells might worsen prognosis (Anderson et al, 1989;Gribben et al, 1991;Brenner et al, 1993;Brugger et al, 1994;Moss et al, 1994). In recent years, especially in breast and colon cancer, it has been shown that occult contamination of the peripheral blood or bone marrow at diagnosis with tumour cells exerts an adverse influence on survival (Berger et al, 1988;Cote et al, 1991;Schlimok et al, 1991;Pantel et al, 1993;Diel et al, 1994;Harbeck et al, 1994;Menard et al, 1994). Often, in these studies, a monoclonal antibody (MAb) or a panel of MAbs directed against tumour cell-surface glycoproteins or cytokeratins was used to detect circulating tumour cells.…”

High-dose chemotherapy, autologous bone marrow or stem cell transplantation and post-transplant consolidation chemotherapy in patients with advanced breast cancer

“…19,20 Keywords: bone marrow; transplantation; breast cancer Given these considerations, we designed a treatment strategy for patients with metastatic breast cancer consisting of high-dose alkylating agent chemotherapy followed by with the goal of eradicating small numbers of malignant period, on days −10 to day −1. Four patients received posttransplant radiation to areas of persistent abnormalities on cells that may have been unknowingly reinfused with the autograft.…”