Quantitative changes in cytological molecular markers during primary medical treatment of breast cancer: A pilot study

Aim: To quantify the changes in biological molecular markers during primary medical treatment in patients with operable breast cancer and to assess th eir possible relationship with response to treatment. Methods: The treatment group consisted of 31 patients with operable breast carcinomas, median age 57 years (range 41 - 67), treated with four 3-weekly cycles of chemotherapy with Mitoxantrone, methotrexate (+/- mitomycin C), and tamoxifen before surgery. Fine needle aspiration (FNA) was used to obta in samples from patients prior to and at 10 or 21 days post-treatment. The following molecular markers were assessed: estrogen receptor (ER), progeste rone receptor (PgR), p53, Bcl-2, and Ki67 measured by immunocytochemistry, and ploidy and S-phase fraction (SPF) by flow cytometry. To evaluate the re producibility of the technique, repeat FNA was performed in a separate non- treatment control group of 20 patients and the same molecular markers asses sed, two weeks after the first sample with no intervening treatment. Results: The non-treatment control group showed a high reproducibility for the measurement of molecular markers from repeat FNA. In the treatment grou p there was a non-significant reduction in SPF and a significant reduction (p = 0.005) in Ki67. Patients who responded to neoadjuvant therapy were mor e likely to have a reduction in these two markers than those who failed to respond. Similarly, a reduction in ER scores was observed between the first and second samples (p = 0.04). For PgR, the change between the first and s econd samples was not significant although there was a significant differen ce between responders and non-responders (p = 0.03). All nine patients with an increase in PgR were responders. No significant changes in p53 or Bcl-2 were observed during treatment. Conclusion: Molecular markers can be adequately measured from FNA samples p rior to and during neoadjuvant therapy. Changes in cellular proliferation a nd hormone receptors have been shown that may be related to tumour response . These relationships should be assessed in a larger cohort of patients.