Changes in proliferation in primary breast cancers during chemoendocrine therapy

The proliferation markers Ki67 and S-phase fraction (SPF) are important biological variables in determining the course of malignant disease. Changes in these variables may provide additional prognostic information. We have studied changes in Ki67 (measured by immunocytochem-istry using the Mib 1 antibody) and SPF (by flow cytometry) on samples obtained by FNA from patients with early breast cancer. In a contrai group of 25 patients repeat FNAs were taken 2 weeks apart, with no intervening treatment, in order to determine the normal variation. For Ki67 the median % + ve for the first sample was 3.0% (range 0–23%) and the second was 4.0% (range 0–23%). For SPF the median for the first sample was 7.8% (range 1.5–21.8%) and for the second 10.3% (range 0.8–22.5%). This demonstrates (i) the good re-producibility of the technique and (ii) that FNA itself does not affect subsequent measurement of proliferation in the same tumour. In 24 patients repeat FNA was performed at 10 or 21 days after chemoendocrine therapy (CET) with Mitozantrone, Methotrexate and tamoxifen. Pre-CET the median Ki67 was 12.9% (range 1–37.7%)andpost-CET 5.5% (range 0–14.7%), P 0.05. Pre-CET the median SPF was 4.1% (range 0.9–27.7%)and the post-CET 3.2% (range 0.4–19.2%), P = NS. These changes in Ki67 may be used as an intermediate marker of response to evaluate the effectiveness of different therapeutic agents in groups of patients. For individuai patients change in relation to response to therapy needs to be evaluated with more patients. Additional quantitative measurement of apoptosis might enhance the biological and clinical significance of these measurements.