Macromolecular interstitial clearance, tumour vascularity, other prognostic factors and breast cancer survival

Clearance of large molecules from the interstitial space is an important function of lymphatics and is affected by local pathologic changes.

To determine if the clearance rate of interstitially injected albumin is correlated to tumour characteristics and outcome in women with invasive breast cancer.

In a consecutive series of women coming to biopsy for suspected breast cancer, technetium-tagged albumin was injected into the tissue adjacent to the palpable mass. The isotope disappearance rate was measured over two hours. Also assessed were the maximum vessel density (MVD-using Factor VIII polyclonal antisera), the proliferation rate (using Ki-67 antisera), node status, tumour size, histologic and nuclear grade, mitotic rate, and p53 and c-erbB-2 oncoproteins. All patients were followed until relapse and for a minimum of 10 years.

In multivariate analysis, an association between relapse-free survival and isotope clearance rate was suggested (p = 0.024). The best outcome was seen in patients with the least isotope clearance. Node status, size, histologic and nuclear grade, and mitotic rate correlated with survival. MVD did not correlate with survival and was inversely related to the isotope clearance rate. Tumour proliferation rate, and the c-erbB-2 and p53 oncoproteins did not relate to outcome.

The role of lymphatics in breast cancer is difficult to study. Measurement of interstitial clearance may be a useful technique and could be a prognostic factor.