In patients with breast cancer, biopsies for lymph node metastases are usually performed to determine the patient prognosis — those who test positive are considered as candidates for adjuvant therapy. However, up to 30% of patients that are free of lymph node metastases still develop metastatic disease. In the New England Journal of Medicine, Stephan Braun et al. report that the detection of disseminated tumour cells in bone marrow samples is a more reliable determinant of metastasis and patient survival.

Unlike other tumour types, such as head and neck cancers, breast tumour cells frequently bypass the lymph nodes and disseminate directly through the blood to distant organs. This haematogeneous dissemination of cancer cells has been shown to be an early event in tumour progression. Small numbers of disseminated tumour cells can be detected in bone marrow samples by sensitive immunocytochemical assays for proteins such as cytokeratin and epithelial mucins, so Braun et al. set out to determine their prognostic significance. In a pooled meta-analysis of data from 9 studies involving 4,703 patients with stage I, II or III breast cancer, the authors evaluated the association between detection of bone marrow micrometastases and patient outcome over a 10-year period.

The study compared the effects of different factors, such as tumour size, grade, bone marrow metastasis, lymph node metastasis and hormone receptor expression, and revealed that the presence of micrometases in bone marrow were the best predictors of outcome (survival, disease recurrence and metastasis to other organs) within the first 5 years after diagnosis. Bone marrow micrometastases were detected in over 30% of patients and these patients were found to develop larger tumours with a higher histological grade that more frequently metastasized to other organs. Furthermore, patients with bone marrow micrometastases were more likely to die of the disease, even among patients that received adjuvant therapy. In patients with very small tumours (less than 2 cm in diameter) without lymph node metastases, and who therefore did not receive adjuvant therapy, the presence of bone marrow micrometastses was also associated with shorter survival times.

The authors suggest that assays for the presence of bone marrow micrometastases could be a complementary approach to lymph node biopsies in determining which patients should receive adjuvant therapy.