Tumor Cells in Marrow Predict Cancer Outcome

HAMBURG—Tumor cell detection (TCD) in bone marrow should supplant axillary lymph node status as a prognostic indicator for women with early breast cancer, Ingo J. Diel, MD, of the University of Heidelberg, said at the Ninth European Cancer Conference (ECCO 9).

Although nodal status currently ranks as the most striking predictor of outcome, some 25% to 30% of women with negative nodes will relapse within 10 years while 30% to 40% of those with positive nodes will be long-term survivors. “So the prognostic value of lymph node status is limited,” he said.

In the Heidelberg study, Dr. Diel and his colleagues have performed immuno-cytologic assays on bone marrow aspirates from nearly 1,300 breast cancer

patients. The bone marrow aspirates were obtained from the iliac crests during surgery and staining was performed using a monoclonal antibody that reacts with the core protein of TAG-12, a tumor-associated glycoprotein expressed by more than 95% of breast cancers.

Analysis has shown that 5-year distant-relapse-free survival is more than 90% for women who are TCD negative, but only around 50% for those who are TCD positive.

The most interesting subgroup of patients, Dr. Diel said, were the 593 women with T1 tumors, 39% of whom were TCD positive. Of the women with early disease who developed metastases during a median follow-up period of 44 months, 79% were TCD positive whereas only 44% were node-positive. Similarly, among patients who died, the incidence of TCD positivity was 71%, while the frequency of node positivity was only 46%.

The differences were highly significant in patients with T1b disease, but were most marked in T1c patients. The Heidelberg investigators found no significant correlations between TCD positivity and nodal status, estrogen receptor status, progesterone receptor status, S-phase fraction, or tumor grade.

The combination of TCD status and nodal status emerged as a particularly powerful predictor of long-term survival in women with early disease, Dr. Diel said. Not unexpectedly, the worst prognosis—30% metastasis-free survival at 10 years—was observed in women with both positive axilla and tumor cells in the bone marrow, while the second worst prognosis (50% survival) was seen in women with negative nodes and positive TCD. Survival was in the neighborhood of 90% for women who were TCD negative, irrespective of their nodal status.

According to a Cox regression analysis, positive axillary nodes double the risk of a bad outcome in women with early-stage breast cancer, whereas tumor cells in the bone marrow multiply the risk by more than eightfold.

Safety is another prime advantage of bone marrow aspiration, Dr. Diel said. He emphasized that the complications of axillary dissection are legion, and may include seromas, dysesthesia of the arm, restriction of mobility, lymphedema, infection, and hemorrhage. In contrast, he said, the only pitfalls of bone marrow aspiration are transient hematoma and, rarely, postoperative pain.

Dr. Diel and his colleagues are now considering a study in which women with small breast tumors would be randomized to have axillary lymphadenectomy followed by standard adjuvant therapy, or to forego lymphadenectomy. Members of the nonlymphadenectomy group would receive adjuvant chemotherapy only if their bone marrow was positive for the presence of tumor cells.